Table 1.
Membrane/Lipid binding proteins involved in cytokinesis.
| Protein Name/Protein Complex | Localization | Predicted/Known Lipid Binding |
Mechanism in Cytokinesis | Ref. |
|---|---|---|---|---|
| ADP-ribosylation factor like protein 2–3 (ARL2, ARL3) | Midbody | N-terminal amphipathic helix/Anionic PLs. | Small GTPase, regulate microtubule dynamics | [170,171] |
| ADP-ribosylation factors (Arf1, Arf3, Arf6) | PM, Golgi, midbody, and endosomes | N-myristoylated | Small GTPases involved in Intra cellular vesicular trafficking, required during furrow ingression and abscission | [172,173] |
| Alix | Endosomes, midbody | Lysobisphosphatidic acid | Recruits ESCRT machinery to abscission site at midbody | [174,175] |
| ANCHR (abscission/NoCut checkpoint regulator; ZFYVE19) | Midbody | PIPs | Regulates the abscission checkpoint via retention of ESCRT component VPS4 at the midbody ring | [176] |
| Anillin | Contractile ring | PI(4,5)P2 | Scaffolds contractile ring at the cell equator | [177,178] |
| Annexin A2; Annexin11 | Cleavage furrow (A2), midbody (A11) | PIPs | AnnexinA2: connects equatorial cortex to central spindle and helps in localization of RhoGEF Ect2; Annexin A11, required for MKLP1 and Aurora B localization to the midbody | [179,180] |
| ARHGAP19 | Cleavage furrow | Anionic PLs | Controls cytokinesis in T lymphocytes by acting as GAP for RhoA | [181] |
| Armadillo protein p007/Plakophilin-4 (PKP4) | Midzone, midbody | Unknown | Interact with RhoA and Ect2 and regulates Rho signaling | [182] |
| Capping protein (CAPZB) | Cleavage furrow | Anionic PLs | Required for midbody maturation, regulates actin dynamics | [183,184] |
| Chronophin/PDXP | Localizes to PM, Cleavage furrow, midbody | Unknown | Regulates cofilin dependent actin dynamics | [185] |
| Citron Rho-interacting kinase (CIT) | Cleavage furrow and midbody | Unknown | Regulates midbody formation | [186] |
| Cofilin-1 | Cleavage furrow and midbody | PI(4,5,)P2 | Regulate actin filament severing | [187,188] |
| ESCRT complex | Midbody | Anionic PLs | Involved in membrane cut during abscission | [189,190,191] |
| Exocyst complex Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84 |
Endosomes, Early, late cleavage furrow and midbody | Sec3 and Exo70 interact PI(4,5)P2 | Tethering of secretory vesicles to plasma membrane | [192,193,194,195] |
| Ezrin, Radixin, Moesin (ERM) proteins | Cholesterol dependent localization to cleavage furrow | PI(4,5,)P2 | Regulate membrane to cytoskeleton interaction | [196,197] |
| F-BAR domain/Cdc15 | Cell middle/contractile ring | Anionic PLs | Interacts with formin Cdc12 and promote contractile ring formation | [65] |
| Gin4 (Nim1 protein kinase) | PIPs | Septin assembly | [198] | |
| Golgi phosphoprotein 3 (GOLPH3) |
Golgi, cleavage furrow | PI4(P) effector | Required for localization of Rab11-positive PI(4)P enriched vesicles at the cleavage furrow | [199] |
| GPCRs | Spindle pole, midzone, midbody | Multi-pass membrane proteins | Affects actin cytoskeleton, knockdown causes defects | [200,201,202] |
| Integrin beta-1 | Rab21 endosomes | Single pass membrane protein | Rab21 mediated integrin trafficking to and from the cleavage furrow | [203] |
| IPIP27 | Endomembranes | PIPs | Scaffolds OCRL and couples it to endocytic BAR domain proteins (SH3PX1 or Pacsin2); involved in PI(4,5,)P2 homeostasis | [204] |
| MICAL (1 and 3) | Intercellular bridge | Unknown | MICAL-L1 and MICAL3 mediate targeting of Rab11-FIP3/Rab35 and Rab8 positive endosomes respectively to the ICB; regulate F-actin levels at midbody | [3] |
| MIT domain containing protein 1 (MITD1) | Late endosomes and midbody | PI(4,5,)P2 | Interacts with ESCRT-III components and mediates abscission | [205] |
| Mso1 (Mint1) and Sec1 (Munc18) | Cell division site | Interact membrane via SNAREs | Vesicle fusion and cargo delivery; CR constriction, disassembly, and membrane closure defects | [206] |
| Myosin 19 (MYO19) | Mitochondria outer membrane | PA, PIP, PIP2 and PIP3 | Involved in mitochondrial segregation via actin-based motor activity | [207,208] |
| Nonmuscle myosin-II | Cleavage furrow/ Contractile ring |
Anionic phospholipids | Directly binds to membranes independent of F-actin | [209] |
| OCRL | Endosomes/intercellular bridge | PI(4,5)P2 | Rab35 dependent localization to ICB, hydrolyze PI(4,5)P2 which in turn help in actin clearance. | [23] |
| Opy1 | Dual PH domain containing protein | PI(4,5)P2 | Endogenous PI(4,5)P2 sensor binds to its3 | [210] |
| P190RhoGAP (ARHGAP35 and ARHGAP5) | Cleavage furrow | Anionic PLs | Regulates RhoA activity | [211,212] |
| P50RhoGAP (ARHGAP1) | Midbody | Anionic PLs | Promote actin clearance in the intercellular bridge | [213] |
| PDZD-8, TEX-2, OCRL and UNC-26/synaptojanin | ER/intracellular membrane compartments | PI(4,5)P2 | Endosomal PI(4,5)P2 homeostasis | [214] |
| PI3K-C2α | Midbody | PI(3,4)P2 | VPS36 binds to PI(3,4)P2 at the midbody and recruits CHAMP4B to mediate abscission | [10] |
| PI3K-III kinase complex (VPS15, VPS34, Beclin1, UVRAG and BIF-1 | Localizes to endosomes and midbody | PI, PIP, N-myristoylation (Vps15) | Phosphorylates PI to PI(3)P; required for abscission | [215,216] |
| Pkd2/polycystins | PM/cell equatorial plane | Transmembrane protein | Membrane stretch activated Ca+ influx | [217] |
| PRIP (phospholipase C (PLC)-related catalytically inactive protein) | Cleavage furrow | PI(4,5)P2 | regulates phosphoinositide metabolism at cleavage furrow | [218] |
| Prostate androgen regulated protein (PAR) | Centrosomes, spindle midzone, midbody | Single pass membrane protein | Form complex with Aurora A, Survivin, Aurora B and INCENP and crease Aurora B kinase activity | [219] |
| Protein kinase C epsilon (PRKCE) | Late cytokinetic furrow | DAG | Required for RhoA inactivation and actomyosin clearance during abscission | [164] |
| PTEN | Cleavage furrow | PI(3,4,5)P2 | Contributes to PI(4,5)P2 production at the furrow. | [93,100] |
| PTEN/dPLCXD | Endosomes | PI(4,5)P2 | Novel PI(4,5)P2 phosphatase, overexpression rescues OCRL loss of function phenotypes | [220] |
| Rab1 | Golgi, cleavage furrow | S-geranylgeranylations | Interact with GOLPH3 and regulates vesicular trafficking | [221] |
| Rab10 | Cleavage furrow midbody | S-geranylgeranylations | Unknown, possibly involved in delivery of Sorcin protein to cleavage site which is involved in regulating calcium homeostasis and Polo-like kinase-1 | [222] |
| Rab14 | Cleavage furrow/midbody | S-geranylgeranylations | Regulate actin clearance at the midbody. | [223,224] |
| Rab21 | Early endosomes, cleavage furrow, midbody | S-geranylgeranylations | Integrin bet-1 trafficking during late steps of cytokinesis | [203] |
| Rab24 | Mitotic spindle, cleavage furrow and intercellular bridge | S-geranylgeranylations | Affects kinetochore-microtubule attachment | [225,226] |
| Rab35 | Recycling endosomes, cleavage furrow, mid body | PIP2, S-geranylgeranylations | PIP2 and F-acting remodeling during late steps of cytokinesis | [23,92,173] |
| Rab7 | Late endosomes, multivesicular bodies | Small GTPase, S-geranylgeranylation | Membrane delivery to cleavage furrow | [131] |
| Rab8 | Midbody | S-geranylgeranylations | Required for abscission | [227] |
| RacGTPase-activating protein-1 (MgcRacGAP) | Cleavage furrow and midbody | Anionic phospholipids | Regulates Rho GTPase | [112] |
| RalA and RalB | RalA (cleavage furrow) RalB midbody | Polybasic motif and S-geranylgeranylation | RalA (exocyst targeting to cleavage furrow); RalB (exocyst targeting to midbody during abscission) | [228,229,230] |
| Ras-related protein Rab11A and Rab11 family interacting protein 3 and 4 | Recycling endosomes, Cleavage furrow midbody |
Rab11 (small GTPase) S-geranylgeranylation | Endocytic traffic during late steps of cytokinesis, | [231,232] |
| Rho GTPase-activating protein 35 (ARHGAP35) | Cleavage furrow | Anionic phospholipids | Regulates actomyosin contractility | [211,212,233] |
| Rho GTPases (RhoA, RhoB, RhoC, Cdc42 and Rac1) | Cleavage furrow | Polybasic motif, S-geranylgeranylation (all), S-palmitoylation (Cdc42, RhoB) and S-farnesylation (RhoB) | Acting cytoskeleton organization, Rho is involved in cleavage furrow formation and ingression | [234] |
| Rho-associated protein kinases 1 and 2 | Midbody | PIP2, PIP3, sphingosine, arachidonic acid, PC | Rho effector kinases. Regulates contraction of actomyosin ring by phosphorylation of myosin light chain | [235,236] |
| RhoGEF ECT2 | Cleavage furrow, midbody | Phosphoinositides | RhoA activation and cleavage furrow formation | [105] |
| Septins (SEPT1-12, SEPT14) | Cleavage furrow, midbody | PI(4,5,)P2 | GTPase, form filaments, rings during cleavage furrow ingression and abscission at midbody; act as diffusional barrier | [237,238] |
| Serine/threonine-protein kinase N2 (PKN2) | Cleavage furrow and midbody | C2 domain, anionic PLs, arachidonic acid | Function as Rho/Rac effector, required for abscission | [239,240] |
| Serologically defined colon cancer antigen (SDCCAG3) | Endosomes, midbody | unknown | Regulate Arf-mediated vesicular trafficking/signaling | [241] |
| SNARE (t-SNAREs include Sso, Sec9,) (v-SNARE Snc1/2) |
Target SNAREs(t-SNARE/syntaxin) Vesicular SNARE (v-SNARE/VAMP) |
Transmembrane proteins | Required for vesicle fusion at the target membranes | [3,242] |
| Sorting nexins (SNX9, SNX18, SNX33) |
PX and BAR domain | PIP, PIP2, PIP3 | Required for endocytosis dependent and independent roles in cytokinesis | [243] |
| Spartin (SPG20) | Lipid droplet and endosomes | unknown | Localizes to midbody by interacting with ESCRT-III protein Ist1 | [244] |
| Spastin (SPAST) | ER, endosomes, midbody | unknown | Involved in microtubule severing during abscission | [245] |
| Spectrin beta chain | PH domain | PIP2, PIP3, PS | Lateral membrane biogenesis in concert with Ankyrin-G | [246] |
| STAM-Binding protein | Endosomes, cleavage furrow, midbody | unknown | Regulation of ubiquitylation at central spindle | [247] |
| Stomatin | Plasma membrane | Cholesterol | Change in lipid species including ether lipids and PC | [248,249] |
| Supervillin | Cleavage furrow midbody | Interact with lipid raft proteins | Links plasma membrane to the cytoskeletion | [250,251,252] |
| Ubiquitin carboxy-terminal hydrolase 8 (USP8) | Endosomes, midbody | Farnesylation ? | Regulation of ubiquitylation at central spindle | [247] |
| UNC119a | Dynamic localization; spindle midzone and midbody | Interact with N-myristoylated proteins | Has role in Fyn signaling and Rab11 dependent phosphorylation at midbody | [253] |
| Ync13/UNC-13/Munc13 | Plasma membrane, cell tip, division site | PS, PIP2 | Coordinates exocytosis, endocytosis, and cell wall integrity | [254] |
| YPP1 and Efr3 | Plasma membrane | Basic residues in Efr3 binds to anionic PLs. | Scaffolds Stt4 (PI4KIIIalpha) | [255,256,257] |
| Zinc-finger FYVE domain-containing protein 26 (ZFYVE26) | midbody | PI(3)P | Interact with ESCRT-III subunits to mediate abscission | [258] |