TABLE 1.
Proteins related to autophagic and endolysosomal processes.
| Protein | UniProt acc.# (name); alternative names | Present in SynProta | Present in Hidden SV Proteomeb | Present in SynGOc | Localization in Synapsed |
Function/Remarks | Selected references |
| AMBRA1 | A2AH22 (AMRA1_MOUSE); Activating molecule in BECN1-regulated autophagy protein 1 | No | No | No | n.d. | Part of the autophagy nucleation complex | (Fimia et al., 2007; Dikic and Elazar, 2018; Tomoda et al., 2020) |
| Annexin A7 | Q07076 (ANXA7_MOUSE), Annexin-7; Synexin | Yes | Yes SV-visitor |
No | Synapse SV |
Autophagy, promotes membrane fusion | (Taoufiq et al., 2020) |
| AP-2 |
P17426 (AP2A1_MOUSE), P17427 (AP2A2_MOUSE), Q9DBG3 (AP2B1_MOUSE), P84091 (AP2M1_MOUSE), P62743 (AP2S1_MOUSE); Adaptor protein AP-2 complex subunits mu, alpha-1, alpha-2, beta1 and sigma |
Yes | Yes SV-resident |
Yes | Synapse, Presynapse, Peri-AZ SV |
Adaptor for Clathrin-mediated membrane fission. Together with CALM, AP-2 mediates formation of autophagosomes/signaling amphisomes; present in SV preparations. | (Boyken et al., 2013; Tian et al., 2014; Weingarten et al., 2014; Kononenko et al., 2017; Wang et al., 2017; Azarnia Tehran et al., 2018; Taoufiq et al., 2020) |
| Arf6 | P62331 (ARF6_MOUSE); ADP-ribosylation factor 6; | Yes | Yes SV-visitor |
Yes | Presynapse Postsynapse SV |
Small GTPase antagonizes Rab35 in SV recycling; regulates autophagy by interplay with Synj1 and/or phospholipase D | (Moreau et al., 2012; George et al., 2016; Sheehan and Waites, 2019) |
| Arl8 | Q9CQW2 (ARL8B_MOUSE); ADP-ribosylation factor-like protein 8B; | Yes (8A,B) | Yes (8A,B) SV-visitor |
(Yes) BP only |
Synapse, Presynapse SV, AZ |
Present in synaptic vesicle (SV) and active zone (AZ) preparations; anterograde transport of lysosome-related vesicles | (Takamori et al., 2006; Boyken et al., 2013; Vukoja et al., 2018; Farfel-Becker et al., 2019; De Pace et al., 2020; Borchers et al., 2021) |
| ATG2a | Q6P4T0 (ATG2A_MOUSE); Autophagy-related protein 2 homolog A; ortholog: D3ZT64 (D3ZT64_RAT, formerly XP_219529) | Yes | (Yes) low abundance P2’-fraction |
No | Synapse, Synaptosome Presynapse, SV |
Present in SV protein preparation; Transfers phospholipids to the phagophore. |
(Takamori et al., 2006) (Soukup et al., 2016; Sawa-Makarska et al., 2020; Chang et al., 2021) |
| ATG3 | Q9CPX6 (ATG3_MOUSE); Autophagy-related protein 3. Ubiquitin-like-conjugating enzyme ATG3; Short name: APG3-like | No | P2’-fraction | No | Synapse | E2-like enzyme of the ubiquitin-like conjugation system; ATG3 can be recruited to membranes by EndoA | (Soukup et al., 2016; Vijayan and Verstreken, 2017; Dikic and Elazar, 2018; Hill and Colon-Ramos, 2020) |
| ATG4 family | Q9U1N6 (ATG42_CAEEL); Q8C9S8 (ATG4A_MOUSE) etc.; Cysteine proteases ATG4A-D | No | No | No | n.d. | Cysteine proteases of the ubiquitin-like conjugation system; C. elegans: A TG-4.2 involved in autophagosome clearance | (Dikic and Elazar, 2018; Hill et al., 2019; Hill and Colon-Ramos, 2020) |
| ATG5 | Q99J83 (ATG5_MOUSE), Autophagy protein 5; APG5-like | No | No | No | Synapse, Presynapse | Part of the ATG12-ATG5-ATG16L1 E3-like complex of the Ubiquitin-like conjugation system; binds AZ protein Bassoon; colocalizes with presynaptic markers in primary neurons; ATG5-KO in neurons induces axonal ER-phagy. | (Vijayan and Verstreken, 2017; Dikic and Elazar, 2018; Tomoda et al., 2020; Andres-Alonso et al., 2021; Chang et al., 2021) (Okerlund et al., 2017; Kuijpers et al., 2021; Soykan et al., 2021) |
| ATG7 | Q9D906 (ATG7_MOUSE); Ubiquitin-like modifier-activating enzyme ATG7; Autophagy-related protein 7; APG7-like | No | P2’-fraction | No | Synapse Synaptosome |
E1-like enzyme of the Ubiquitin-like conjugation system; ATG7 deficiency has severe effects on presynaptic function. |
(Komatsu et al., 2007; Vijayan and Verstreken, 2017; Dikic and Elazar, 2018; Lieberman and Sulzer, 2020; Overhoff et al., 2021) |
| ATG9A | Q68FE2 (ATG9A_MOUSE); Autophagy-related protein 9A; APG9-like 1; | Yes | Yes SV-resident |
Yes | Synapse, Presynapse; SV, AZ, Peri-AZ |
Lipid scramblase involved in autophagosome biogenesis; present in SV preparations (SV-resident repertoire); likely to be involved in SV autophagy. | (Boyken et al., 2013; Stavoe et al., 2016; Guardia et al., 2020; Hill and Colon-Ramos, 2020; Maeda et al., 2020; Sawa-Makarska et al., 2020; Chang et al., 2021) |
| ATG10 | Q8R1P4 (ATG10_MOUSE); Ubiquitin-like-conjugating enzyme ATG10; Autophagy-related protein 10 | No | No | No | n.d. | E2-like enzyme of the ubiquitin-like conjugation system; conjugates ATG12 on ATG5. | (Dikic and Elazar, 2018; Stavoe and Holzbaur, 2019) |
| ATG12 | Q9CQY1 (ATG12_MOUSE); Ubiquitin-like protein ATG12; Autophagy-related protein 12; APG12-like | No | No | No | n.d. | Part of the ATG12-ATG5-ATG16L1 E3-like complex of the Ubiquitin-like conjugation system; | (Vijayan and Verstreken, 2017; Dikic and Elazar, 2018; Chang et al., 2021) |
| ATG13 | Q91YI1 (ATG13_MOUSE); Autophagy-related protein 13 | No | No | No | n.d. | Adaptor protein within the ULK/ATG1 complex | (Dikic and Elazar, 2018; Hill and Colon-Ramos, 2020; Tomoda et al., 2020) |
| ATG14/ATG14L | Q8CDJ3 (BAKOR_MOUSE) Beclin 1-associated autophagy-related key regulator; Autophagy-related protein 14-like protein | No | No | No | n.d. | Part of the PIK3C3 complex; and promotes autophagosome-endolysosome fusion. | (Diao et al., 2015; Dikic and Elazar, 2018; Hill and Colon-Ramos, 2019) |
| ATG16L1 | Q8C0J2 (A16L1_MOUSE); Autophagy-related protein 16-1; APG16-like 1 | Yes | Yes SV-visitor |
No | Synapse; Presynapse, SV |
Part of the ATG12-ATG5-ATG16L1 E3-like complex of Ub-like conjugation system; may be linked to SV autophagy. | (Binotti et al., 2015; Dikic and Elazar, 2018; Hill and Colon-Ramos, 2020; Chang et al., 2021) |
| ATG101 | Q9D8Z6 (ATGA1_MOUSE); Q9VWQ1 (Q9VWQ1_DROME); Autophagy-related protein 101 | No | P2’-fraction | No | Synapse Synaptosome |
Part of the ULK/ATG1 complex | (Dikic and Elazar, 2018; Chang et al., 2021) |
| ATL2/3 |
Q6PA06 (ATLA2_MOUSE); Atlastin-2; ADP-ribosylation factor-like protein 6-interacting protein 2; Q91YH5 (ATLA3_MOUSE); Atlastin-3 |
Yes (ATL2) | Yes ATL2: SV-visitor ATL3: SV-visitor |
No | Synapse, Presynapse SV |
Recruitment and stabilization of ATG1 complex at the FIP200-ATG13–specified autophagosome formation sites on ER. Adaptor for ER-phagy; required for presynaptic function at larval NMJ. |
(De Gregorio et al., 2017; Andres-Alonso et al., 2021; Liu et al., 2021; Wojnacki et al., 2021) |
| BAG3 | Q9JLV1 (BAG3_MOUSE); BAG family molecular chaperone regulator 3; Bcl-2-associated athanogene 3 | Yes | P2’-fraction | No | Synapse Synaptosome |
Co-chaperonin for HSC70, interacts with synaptopodin | (Sturner and Behl, 2017; Ji et al., 2019) |
| Bassoon | O88737 (BSN_MOUSE); AZ scaffold protein Bassoon. | Yes | Yes SV-visitor |
Yes | Presynapse, AZ, SV |
Recruits ATG5 to the presynaptic AZ; functionally interacts with Parkin. | (Okerlund et al., 2017; Vijayan and Verstreken, 2017; Hill and Colon-Ramos, 2020; Hoffmann-Conaway et al., 2020; Andres-Alonso et al., 2021) |
| Beclin-1/ATG6 | O88597 (BECN1_MOUSE), Beclin-1 | No | Yes SV-visitor |
No | Presynape SV |
Core subunit of the PI3KinaseC3 complex; regulates Vps34 lipid kinase; | (Dikic and Elazar, 2018) |
| CALM/PICALM | Q7M6Y3 (PICAL_MOUSE); Phosphatidylinositol-binding Clathrin assembly protein; Clathrin assembly lymphoid myeloid leukemia | Yes | Yes SV-visitor |
Yes | Presynapse; Peri-AZ, SV |
Autophagic sorting adaptor; endocytic adaptor; | (Takamori et al., 2006; Tian et al., 2013; Azarnia Tehran et al., 2018) |
| CISD2 | Q9CQB5 (CISD2_MOUSE); CDGSH iron-sulfur domain-containing protein 2; Miner 1; NAF-1 | No | Yes SV-visitor |
No | Presynapse SV |
Regulator of autophagy; contributes to control of Beclin-1. | (Chang et al., 2010; Shen et al., 2021) |
| DFCP1/Zfyve1 | Q810J8 (ZFYV1_MOUSE); Zinc finger FYVE domain-containing protein 1 | No | Yes SV-visitor |
No | Presynapse SV |
PI3P- binding protein; enriched in omegasomes of the ER | (Dikic and Elazar, 2018; Hill and Colon-Ramos, 2020) |
| DENND3 | A2RT67 (DEND3_MOUSE); DENN domain-containing protein 3 | No | No | No | n.d. | Actin-binding guanine nucleotide exchange factor for Rab12 activated by ULK1 and required for autophagy | (Xu et al., 2015, 2018; Wojnacki and Galli, 2018; Wei and Duan, 2019) |
| Endophilin-A/EndoA | Q62420 (SH3G2_MOUSE); Endophilin A1, A2; Q8T390 (SH3G3_DROME); Endophilin-A; SH3 domain-containing GRB2-like protein; | Yes | Yes SV-visitor |
Yes | Presynapse; SV Peri-AZ |
Endocytic adaptor essential for SV recycling; forms docking stations for autophagic proteins at synapses. | (Murdoch et al., 2016; Soukup et al., 2016, 2018; Vijayan and Verstreken, 2017; Azarnia Tehran et al., 2018) |
| Endophilin-B1 | Q9JK48 (SHLB1_MOUSE); SH3 domain-containing GRB2-like protein B1; BIF-1 | No | Yes SV-visitor |
No | Presynapse, SV, |
Associates with PI3KC3-C2 and regulates ATG9a trafficking | (Takahashi et al., 2011; Taoufiq et al., 2020) |
| FADD | Q61160 (FADD_MOUSE); FAS-associated death domain protein | No | No | No | n.d. | Death domain protein that directly interacts with ATG5, | (Pyo et al., 2005) |
| FAM134B | Q8VE91 (RETR1_MOUSE); Reticulophagy regulator 1; family with sequence similarity 134 member B; | No | No | No | n.d. | Adaptor for ER-phagy | (Khaminets et al., 2015; Stavoe and Holzbaur, 2019; Andres-Alonso et al., 2021) |
| FIP200/Rb1cc1 | Q9ESK9 (RBCC1_MOUSE); RB1-inducible coiled-coil protein 1; FAK family kinase-interacting protein of 200 kDa | Yes | P2’-fraction | No | Synapse, Synaptosome |
Part of the ULK/ATG1 complex | (Dikic and Elazar, 2018; Lieberman and Sulzer, 2020; Tomoda et al., 2020) |
| FBXO32 | Q9CPU7 (FBX32_MOUSE); F-box only protein 32; Atrogin-1 | No | No | No | n.d. | E3-ubiquitin ligase; interacts with endophilin-A to control autophagosome formation and protein homeostasis. | (Murdoch et al., 2016; Azarnia Tehran et al., 2018) |
| GABARAPs/ ATG8-like |
Q9DCD6 (GBRAP_MOUSE); GABA receptor associated protein; Q8R3R8 (GBRL1_MOUSE); P60521 (GBRL2_MOUSE); GABARP-like 1, 2; LGG-1 and LGG-2 in C. elegans | Yes GABARAPL1 GABARAPL2 |
GABARAP, GABARAPL1, GABARAPL2 P2’-fraction |
No | Synapse, Synaptosome Presynapse |
Lipidated ATG8-like proteins that are key factors for various autophagic processes. In C. elegans localized in presynapse |
(Dikic and Elazar, 2018; Hill et al., 2019; Martens and Fracchiolla, 2020) |
| HSC70 | P63017 (HSP7C_MOUSE); Heat shock cognate 71 kDa protein; Heat shock 70 kDa protein 8 (Hspa8) | Yes | Yes SV-visitor |
Yes | Synapse, Presynapse | Cytosolic protein guiding KEFRQ-proteins to chaperone-mediated autophagy (CMA) | (Uytterhoeven et al., 2015; Kaushik and Cuervo, 2018; Andres-Alonso et al., 2021) |
| HOPS complex Vps11 Vps16/Vps33A Vps18 Vps39 Vps41 |
Q91W86 (VPS11_MOUSE) Q920Q4 (VPS16_MOUSE) Q9D2N9 (VP33A_MOUSE) Q8R307 (VPS18_MOUSE) Q8R5L3 (VPS39_MOUSE) Q5KU39 (VPS41_MOUSE); VAM2 |
Yes Yes Yes Yes Yes Yes |
Yes SV-visitor Yes SV-visitor Yes SV-visitor Yes SV-visitor P2’-fraction P2’-fraction |
Yes Yes No Yes No No |
Presynapse, AZ Presynapse Presynapse Presynapse Synaptosome Synaptosome |
Homotypic fusion and vacuole protein sorting complex; involved in the fusion events of late endosomes and lysosomes. | (Jiang et al., 2014; Dikic and Elazar, 2018; van der Beek et al., 2019) |
| Huntingtin/Htt | P42859 (HD_MOUSE), Huntington disease protein homolog; | Yes | Yes SV-visitor |
Yes | Synapse, Presynapse; SV | Scaffolding adaptor recruited to autophagosomes | (Deng et al., 2017; Stavoe and Holzbaur, 2018; Cason et al., 2021) |
| JIP1 | Q9WVI9 (JIP1_MOUSE); c-Jun-amino-terminal kinase-interacting protein 1; JNK-interacting protein 1; Islet brain 1 [IB-1] | Yes | No | No | Synapse (Axon) |
Motor adaptor for autophagosome | (Saudou and Humbert, 2016; Stavoe and Holzbaur, 2018; Hill and Colon-Ramos, 2020; Cason et al., 2021) |
| JIP3 | Q9ESN9 (JIP3_MOUSE); C-Jun-amino-terminal kinase-interacting protein 3; Unc-16; Mapk8ip3 | Yes | P2’-fraction | No | Synapse Synaptosome (Axon) |
Motor adaptor for autophagosome | (Hill et al., 2019; Hill and Colon-Ramos, 2020; Cason et al., 2021) |
| LAMP1, |
P11438 (LAMP1_MOUSE); Lysosome-associated membrane glycoprotein 1; CD107 antigen-like family member A |
Yes | Yes SV-visitor |
Yes | Presynapse, SV |
Marker for degradative autophagy-lysosomal organelles | (De Leo et al., 2016; Vukoja et al., 2018; Hill and Colon-Ramos, 2020) but see also (Cheng et al., 2015) |
| LAMP2(A) |
P17047 (LAMP2_MOUSE); Lysosome-associated membrane glycoprotein 2; CD107 antigen-like family member B |
No | Yes SV-visitor |
No | Presynapse, SV |
LAMP2A is chiefly involved in CMA | (Wang et al., 2017; Issa et al., 2018; Kaushik and Cuervo, 2018) |
| LC3/ATG8 | Q9CQV6 (MLP3B_MOUSE); Autophagy-related ubiquitin-like modifier LC3 B; Microtubule-associated proteins 1A/1B light chain 3B; Map1lc3b. | Yes | Yes SV-visitor |
Yes | Synapse, Presynapse | Lipidated ATG8-like proteins that are key factors for various autophagic processes; LGG in C. elegans; | (Dikic and Elazar, 2018; Hill and Colon-Ramos, 2020; Martens and Fracchiolla, 2020) |
| LRRK1 | Q3UHC2 (LRRK1_MOUSE); Leucine-rich repeat serine/threonine-protein kinase 1 | No | No | No | – | Regulates autophagy via TBC1D2-dependent Rab7 inactivation | (Toyofuku et al., 2015) |
| LRRK2 | Q5S006 (LRRK2_MOUSE); Leucine-rich repeat serine/threonine-protein kinase 2; Dardarin | Yes | No | Yes | Synapse, Presynapse | LRRK2 acts on key actors of the SV cycle; among them endophilin A, a main anchor for autophagic proteins | (Soukup et al., 2016, 2018; Azarnia Tehran et al., 2018; Taylor and Alessi, 2020; Piccoli and Volta, 2021) |
| mTOR | Q9JLN9 (MTOR_MOUSE); Serine/threonine-protein kinase mTOR; mechanistic target of rapamycin; | Yes | Yes SV-visitor |
Yes | Synapse, Postsynapse SV fraction |
Regulates various cellular processes including autophagy | (Bockaert and Marin, 2015) |
| MYCBP2 | Q7TPH6 (MYCB2_MOUSE); E3 ubiquitin-protein ligase MYCBP2; Pam/highwire/rpm-1 protein | Yes | Yes SV-visitor |
No | Presynapse SV fraction |
E3 ligase upstream of ULK1/Unc51 | (Grill et al., 2016; Crawley et al., 2019) |
| NBR1 | P97432 (NBR1_MOUSE); Next to BRCA1 gene 1 protein | No | No | No | – | Autophagy receptor | (Kirkin et al., 2009; Deng et al., 2017; Dikic and Elazar, 2018) |
| NDP52 | A2A6M5 (CACO2_MOUSE); Calcium-binding and coiled-coil domain-containing protein 2; Nuclear domain 10 protein 52 | No | No | No | – | Autophagy receptor | (Deng et al., 2017; Dikic and Elazar, 2018; Chang et al., 2021) |
| NRBF2 | Q8VCQ3 (NRBF2_MOUSE) Nuclear receptor-binding factor 2 | No | No | No | – | Assembles with PI3KC3, Autophagosome maturation, Rab7 effector | (Cai et al., 2021) |
| OPTN | Q8K3K8 (OPTN_MOUSE) Optineurin | No | No | No | – | Autophagy receptor | (Deng et al., 2017; Dikic and Elazar, 2018; Chang et al., 2021) |
| OCRL | Q6NVF0 (OCRL_MOUSE) Inositol polyphosphate 5-phosphatase OCRL | No | Yes SV-visitor |
No | Presynapse SV fraction |
Lipid phosphatase, controls autophagosome-lysosome fusion | (De Leo et al., 2016; Marat and Haucke, 2016; Palamiuc et al., 2020) |
| Parkin | Q9WVS6 (PRKN_MOUSE); E3 ubiquitin-protein ligase parkin | Yes | No | Yes | Synapse, Presynapse, SV |
E3 ubiquitin-protein ligase involved in mitophagy and together with Bassoon controls SV protein degradation. | (Mouatt-Prigent et al., 2004; Dikic and Elazar, 2018; Soukup et al., 2018; Hoffmann-Conaway et al., 2020) |
| p62/SQSTM1 | Q64337 (SQSTM_MOUSE) Sequestosome-1, Ubiquitin-binding protein p62 | No | P2’-fraction | No | Synapse, Synaptosome Presynapse |
Autophagy receptor Presynaptic localization in primary neurons. |
(Deng et al., 2017; Dikic and Elazar, 2018; Soukup et al., 2018) (Okerlund et al., 2017) |
| p115/Uso1 | Q9Z1Z0 (USO1_MOUSE), General vesicular transport factor p115; Protein USO1 homolog; Transcytosis-associated protein | Yes | P2’-fraction | No | Synapse, Synaptosome |
Associates with PI3KC3complex I | (Dikic and Elazar, 2018) |
| PHLPP1 | Q8CHE4 (PHLP1_MOUSE), Pleckstrin homology domain leucine-rich repeat-containing protein phosphatase 1; PH domain-containing family E member 1 | No | No | No | n.d. | Phosphatase in CMA; dephosphorylates e.g., AKT1 |
(Arias et al., 2015; Kaushik and Cuervo, 2018) |
| PLEKHG5 | Q66T02 (PKHG5_MOUSE) Pleckstrin homology domain-containing family G member 5; Synectin-binding RhoA exchange factor; Tech | Yes | No | (Yes) only BP |
Presynapse | Regulates autophagy of SV; Guanine exchange factor (GEF) that regulates the activity of Rab26. | (Lüningschrör et al., 2017; Hill and Colon-Ramos, 2020; Andres-Alonso et al., 2021) |
| PLEKHM1 | Q7TSI1 (PKHM1_MOUSE); Pleckstrin homology domain-containing family M member 1 | No | No | No | n.d. | Rab7 and Arl8 effector; recruits HOPS complex to autophagosome | (Hill and Colon-Ramos, 2020; Andres-Alonso et al., 2021; Borchers et al., 2021) |
| Rab7 | P51150 (RAB7A_MOUSE), Ras-related protein Rab-7a | Yes | Yes SV-Visitor |
Yes | Presynapse, SV |
Small GTPase with key role for the maturation of late endosomes and autophagosomes | (Hyttinen et al., 2013; Weingarten et al., 2014; Hill and Colon-Ramos, 2020; Borchers et al., 2021; Xing et al., 2021) |
| Rab11a | P62492 (RB11A_MOUSE); Ras-related protein Rab-11A | No | Yes SV-visitor |
Yes | Postsynapse Presynapse SV |
Rab of recycling endosomes (RE); involved in phagophore formation from RE | (Binotti et al., 2016; Puri et al., 2018; Wei and Duan, 2019) |
| Rab12 | P35283 (RAB12_MOUSE); Ras-related protein Rab-12 | No | Yes SV-visitor |
No | Presynapse, SV |
Rab involved in autophagy initiation; LRRK2 substrate | (Takamori et al., 2006; Matsui and Fukuda, 2013; Wei and Duan, 2019; Taoufiq et al., 2020) |
| Rab24 | P35290 (RAB24_MOUSE); Ras-related protein Rab-24; Rab-16; | Yes | Yes SV-visitor |
No | Synapse Presynapse SV |
Facilitates clearance of autophagic compartments; | (Yla-Anttila et al., 2015; Wei and Duan, 2019) |
| Rab26 | Q504M8 (RAB26_MOUSE); Ras-related protein Rab26 | Yes | Yes SV-resident |
Yes | Synapse Presynapse, SV |
Links SV to autophagy pathway; in complex with Plekhg5; | (Binotti et al., 2015; Lüningschrör et al., 2017; Wang et al., 2017; Andres-Alonso et al., 2021; Kohrs et al., 2021) |
| Rab35 | Q6PHN9 (RAB35_MOUSE); Ras-related protein Rab-35 | Yes | Yes SV-visitor |
Yes | Synapse, Presynapse, SV |
Small GTPase controlling SV turnover; acts via NDP52 | (Sheehan et al., 2016; Minowa-Nozawa et al., 2017; Soukup et al., 2018; Wei and Duan, 2019) |
| Rab37 | Q9JKM7 (RAB37_MOUSE); Ras-related protein Rab-37 | Yes | Yes SV-visitor |
No | Synapse Presynapse SV |
Interacts with ATG5 and regulates ATG5-12-16 complex assembly | (Sheng et al., 2018; Wei and Duan, 2019) |
| Rab39a | Q8BHD0 (RB39A_MOUSE); Ras-related protein Rab-39A | Yes | Yes SV-visitor |
No | Presynapse SV |
Interacts with PIK3C3 and negatively regulates autophagosome formation; | (Behrends et al., 2010; Boyken et al., 2013; Seto et al., 2013) |
| RHEB | Q921J2 (RHEB_MOUSE); GTP-binding protein Rheb; Ras homolog enriched in brain | Yes | Yes SV-visitor |
Yes | Postsynapse Preynapse SV |
Small GTPase in mTORC1 signaling pathway | (Bockaert and Marin, 2015) |
| RTN3 | Q9ES97 (RTN3_MOUSE); Reticulon-3; | Yes | Yes SV-visitor |
Yes | Presynapse SV |
ER protein involved in ER-phagy | (Weingarten et al., 2014; Grumati et al., 2018; Beese et al., 2019; Stavoe and Holzbaur, 2019; Kuijpers et al., 2021; Wojnacki et al., 2021) |
| RUSC2 | Q80U22 (RUSC2_MOUSE); RUN and SH3 domain-containing protein 2; Iporin | No | No | No | n.d. | Regulates association of ATG9a with kinesin motor | (Guardia et al., 2021) |
| SIPA1L2 | Q80TE4 (SI1L2_MOUSE); Signal-induced proliferation-associated 1-like protein 2; SPAR2 | Yes | P2’-fraction | No | Synaptosome Presynapse |
Rap-GTPase activating protein (RapGAP); component of signaling amphisome; co-traffics with Snapin; colocalized with synaptophysin in presynapses. | (Andres-Alonso et al., 2019, 2021) |
| SNAP29 | Q9ERB0 (SNP29_MOUSE); Synaptosomal-associated protein 29, | Yes | Yes SV-resident |
Yes | Presynapse, SV |
Autophagosome fusion with endolysosome | (Itakura et al., 2012; Diao et al., 2015; Andres-Alonso et al., 2021) |
| Snapin | Q9Z266 (SNAPN_MOUSE); SNARE-associated protein Snapin; Biogenesis of lysosome-related organelles complex 1 subunit 7; BLOC-1S7. | Yes | P2’-fraction | Yes | Synaptosome Presynapse |
Motor adaptor that coordinates retrograde transport and late endosomal-lysosomal trafficking |
(Cai et al., 2010; Kuijpers et al., 2020; Andres-Alonso et al., 2021) |
| SNX4 | Q91YJ2 (SNX4_MOUSE); Sorting nexin-4; ATG24 | Yes | (Yes) P2’-fraction |
Yes | Synaptosome Presynaptic endosome SV |
Phosphatidylinositol 3-phosphate-binding protein that controls ATG9A recycling and autophagy | (Ravussin et al., 2021) |
| Synaptojanins | Q8CHC4 (SYNJ1_MOUSE); Q9D2G5 (SYNJ2_MOUSE); Synaptojanin-1, -2; Synaptic inositol 1,4,5-trisphosphate 5-phosphatase 1, 2. | Yes (both isoforms) | Yes (Synj1) SV-visitor |
Yes (both isoforms) | Presynapse SV fraction |
Lipid phosphatase that is essential for maturation of autophagosmes in presynaptic boutons | (Vanhauwaert et al., 2017; Azarnia Tehran et al., 2018; Soukup et al., 2018) |
| Synaptopodin | Q8CC35 (SYNPO_MOUSE); | Yes | Yes SV-visitor |
Yes | Postsynapse Presynapse? SV |
In cooperation with BAG3 affects fusion between autophagosomes and lysosomes. | (Ji et al., 2019; Taoufiq et al., 2020) |
| Stx17 | Q9D0I4 (STX17_MOUSE); Syntaxin-17; | No | Yes SV-visitor |
No | SV fraction | Autophagosome fusion with endolysosome | (Itakura et al., 2012; Jiang et al., 2014; Diao et al., 2015; Andres-Alonso et al., 2021) |
| Tax1bp1 | Q3UKC1 (TAXB1_MOUSE); Tax1-binding protein 1 homolog | No | P2’-fraction | No | Synaptosome | Autophagy receptor; Ubiquitin-binding protein that mediates autophagosome induction | (Whang et al., 2017; Chang et al., 2021) |
| TBC1D24/ Skywalker |
Q3UUG6 (TBC24_MOUSE); TBC1 domain family member 24; Q9VIH7 (SKY_DROME); GTPase-activating protein skywalker | Yes | P2’-fraction | Yes | Synapse Presynapse |
GTPase activating protein controlling SV turnover; acts on Rab35; regulates autophagy via TRAPP complex and ATG9 | (Fernandes et al., 2014; Lamb et al., 2016; Soukup et al., 2018; Soykan et al., 2021) |
| TBC1D2 | B1AVH7 (TBD2A_MOUSE); TBC1 domain family member 2A; Armus | No | No | (Yes) only BP |
Synapse | GTPase-activating protein for RAB7A | (Toyofuku et al., 2015; Jaber et al., 2016) |
| TBK1 | Q9WUN2 (TBK1_MOUSE); Serine/threonine-protein kinase TBK1; TANK-binding kinase 1 | Yes | P2’-fraction | No | Synapse | Regulates together with Rab35 NDP52 recruitment to promote mitophagy and maturation of autophagosomes. | (Minowa-Nozawa et al., 2017) |
| Tecpr1 | Q80VP0 (TCPR1_MOUSE) Tectonin beta-propeller repeat-containing protein 1 | No | Yes SV-resident |
No | Presynapse SV |
Autophagosome maturation mediated by TECPR1 and the ATG12-ATG5 conjugate; | (Chen et al., 2012; Wetzel et al., 2020) |
| TRAPP complex TRAPPC8 | Q9Y2L5 (TPPC8_HUMAN); Trafficking protein particle complex 8 | No | Yes SV-resident |
No | Presynapse SV |
TRAPPC8 is the mammalian ortholog a yeast autophagy-specific TRAPP subunit. It interacts with TBC1D24 to regulate ATG9 trafficking; | (Lamb et al., 2016) |
| Tsc2 | Q61037 (TSC2_MOUSE); Tuberin; Tuberous sclerosis 2 protein homolog | Yes | P2’-fraction | Yes | Synapse Synaptosome Postsynapse |
Controls mTORC1 signaling; TSC2 is regulated by WIPI3 and FIP200; heterozygous loss of TSC2 function impairs spine development. | (Tang et al., 2014; Bakula et al., 2017; Dikic and Elazar, 2018; Tomoda et al., 2020) |
| Ubqln2 | Q9QZM0 (UBQL2_MOUSE) Ubiquilin-2; Chap1; DSK2 homolog; PLIC-2 | No | P2’-fraction | No | Synaptosome | Ubiquitn binding autophagy receptor | (Deng et al., 2017; Lin et al., 2021) |
| ULKs/ATG1-like ULK1 ULK2 ULK3 |
O70405 (ULK1_MOUSE); Unc51-like kinase 1; Serine/threonine-protein kinase ULK1//Q9QY01 (ULK2_MOUSE); Unc-51-like kinase 2 | No | (Yes) ULK3 P2’-fraction |
No | Synaptosome (SV) |
Initiation of autophagy; ULK2 has important role for excitation-inhibition balance in the brain | (Lee and Tournier, 2011; Alers et al., 2012; Dikic and Elazar, 2018; Sumitomo et al., 2018; Tomoda et al., 2020; Chang et al., 2021) |
| Uvrag | Q8K245 (UVRAG_MOUSE); UV radiation resistance-associated protein | No | Yes SV-visitor |
No | Presynapse SV |
Regulatory component of PIK3C2; involved in maturation of autophagosomes; | (Mercer and Tooze, 2021) |
| VAMP7 | P70280 (VAMP7_MOUSE); Vesicle-associated membrane protein 7; Synaptobrevin-like protein 1; TI-VAMP | Yes | Yes SV-resident |
Yes | Presynapse SV |
Overlapping functions with VAMP8, SNARE of secretory lysosomes in astrocytes. | (Verderio et al., 2012; Toyofuku et al., 2015; Hill and Colon-Ramos, 2020; Tian et al., 2021; Wojnacki et al., 2021) |
| VAMP8 | O70404 (VAMP8_MOUSE); Vesicle-associated membrane protein 8 | No | No | No | n.d. | SNARE involved in autophagosome fusion with endolysosome together with STX17 and SNAP29 | (Itakura et al., 2012; Diao et al., 2015; Andres-Alonso et al., 2021; Tian et al., 2021) |
| Vps13 (a,c,d) | Q5H8C4 (VP13A_MOUSE); Vacuolar protein sorting-associated protein 13A | No | Yes (13d) P2’-fraction (13a,c) |
No | Synaptosome Presynapse SV |
ATG2-like protein involved in ER-phagy. | (Chen et al., 2020; Chang et al., 2021) |
| Vps15/PIK3R4 | Q8VD65 (PI3R4_MOUSE); Phosphoinositide 3-kinase regulatory subunit 4; | No | Yes SV-visitor |
No | Presynapse SV |
Regulatory subunit in the PI3KC3 complex; | (Mercer and Tooze, 2021) |
| Vps33B | P59016 (VP33B_MOUSE); Vacuolar protein sorting-associated protein 33B | No | Yes SV-visitor |
Yes | Presynapse, SV |
belongs to class C core vacuole/endosome tethering (CORVET) complex, which is mainly implicated in endosomal fusion | (Takamori et al., 2006; Jiang et al., 2014; van der Beek et al., 2019) |
| Vps34/PIK3C3 | Q6PF93 (PK3C3_MOUSE); Phosphatidylinositol 3-kinase catalytic subunit type 3; Vps34 | No | Yes SV-resident |
No | Presynapse SV |
Catalytic component of PIK3C3–C1; colocalizes with synaptophysin at synapses. | (Inaguma et al., 2016; Jaber et al., 2016; Dikic and Elazar, 2018) |
| Vps35 | Q9EQH3 (VPS35_MOUSE); Vacuolar protein sorting-associated protein 35; Vesicle protein sorting 35 | Yes | P2’-fraction | Yes | Synapse Synaptosome Presynapse, Peri-AZ |
Component of the retromer complex; involved in SV endocytosis in cooperation with LRRK2. Knock-down causes accumulation of ATG9a on endolysosomes | (Inoshita et al., 2017; Kaushik and Cuervo, 2018; Ravussin et al., 2021) |
| WDFY3/ALFY | Q6VNB8 (WDFY3_MOUSE), WD repeat and FYVE domain-containing protein 3, Autophagy-linked FYVE protein | No | Yes SV-visitor |
No | Presynapse SV |
Autophagy receptor; mainly for aggrephagy, | (Deng et al., 2017; Stavoe and Holzbaur, 2019) |
| WDR47 | Q8CGF6 (WDR47_MOUSE); WD repeat-containing protein 47; Neuronal enriched MAP interacting protein | Yes | P2’-fraction | No | Synapse Synaptosome |
Negatively regulates association of ATG9a with kinesin motor; essential for autophagy | (Kannan et al., 2017; Tomoda et al., 2020; Guardia et al., 2021) |
| WDR91 | Q7TMQ7 (WDR91_MOUSE); WD repeat-containing protein 91 | Yes | No | No | Synapse | Rab7 effector, regulates lysosome fusion. | (Borchers et al., 2021; Xing et al., 2021) |
| WIPI2/ATG18a | Q80W47 (WIPI2_MOUSE); WD repeat domain phosphoinositide-interacting protein 2 | No | P2’-fraction | No | Synapse, Synaptosome |
Involved in early steps of phagophore formation, recruits ATG12-ATG5-ATG16L1 E3-like complex. | (Vanhauwaert et al., 2017; Dikic and Elazar, 2018; Stavoe et al., 2019) |
| WIPI3/WDR45B WIPI4/WDR45 |
Q9CR39 (WIPI3_MOUSE) Q91VM3 (WIPI4_MOUSE); WD repeat domain phosphoinositide-interacting protein 3/4; WD repeat-containing protein 45/45B |
No | P2’-fraction | No | Synaptosome | Components of the autophagy machinery | (Bakula et al., 2017; Wan et al., 2020) |
AZ, active zone; BP, annotated for biological processes; CMA, chaperone-mediated autophagy; SV, synaptic vesicle; n.d., not detected in synapses; P2’, Synaptosomal Protein Preparation (Taoufiq et al., 2020).
bAs reported by Taoufiq et al. (2020).
dAs taken from the databases or as referred to in remarks/function column.