REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
AT8 (1:250)	ThermoFisher	Cat# MN1020
AT8-Biotin (1:1000)	ThermoFisher	Cat# MN1020B
pS422 (1:400)	ThermoFisher	Cat# 44-764-G
HT7 (1:1000)	ThermoFisher	Cat# MN1000
Pan-tau (1:2000)	DAKO	Cat# A0024
NeuN (1:500)	Abcam	Cat# Ab177487
FK2 (1:500)	Merck	Cat# 04-263
GAPDH (1:2000)	Cell Signaling Technology	Cat# 14C10
CypB (1:500)	Santa Cruz Biotechnology	Cat# Sc-130626
β-actin (1:2000)	Santa Cruz Biotechnology	Cat# Sc-47778
β-III-tubulin (1:500)	Abcam	Cat# Ab78078
P62 (1:1000)	ThermoFisher	Cat# PA5-20839
MAP2 (1:1000)	Abcam	Cat# Ab5392
GFP (Venus) – (1:1000)	Proteintech	Cat# 50430-2-AP
Anti-rabbit Alexa 488 (1:1000)	ThermoFisher	Cat# A-11008
Anti-rabbit Alexa 568 (1:1000)	ThermoFisher	Cat# A-11011
Anti-rabbit Alexa 647 (1:1000)	ThermoFisher	Cat# A-21245
Anti-mouse Alexa 488 (1:1000)	ThermoFisher	Cat# A-11001
Anti-mouse Alexa 568 (1:1000)	ThermoFisher	Cat# A-11031
Anti-mouse Alexa 647 (1:1000)	ThermoFisher	Cat# A-21235
Streptavidin Alexa 647 (1:1000)	ThermoFisher	Cat# S32357
Anti-mouse-HRP	ThermoFisher	Cat# A16066
Anti-rabbit-HRP	ThermoFisher	Cat# 65-6120
Bacterial and virus strains
BL-21 (DE3)	Agilent Technologies	Cat# 200131
Rosetta 2 DE3	Novagen	Cat# 71397
XL Gold Ultracompetent Cells	Agilent	Cat# 200314
AAV PHP.eB	Addgene	Cat# 103005
AAV 9P31	Nonnenmacher et al.31	N/A
Chemicals, peptides, and recombinant proteins
T4455	Sigma-Aldrich	Cat# T4455
MG132	Sigma-Aldrich	Cat# M7449
NMS-873	Selleckchem	Cat# S7285
TAK-243	Selleckchem	Cat# S8341
PR-619	Sigma-Aldrich	Cat# 662141
Bafilomycin	Selleckchem	Cat#S1413
0N4R P301S tau	This paper	N/A
0N4R P301S tau-RING	This paper	N/A
Biological samples
AD human brain	Oxford Brain Bank	N/A
PSP human brain	Cambridge Brain Bank	N/A
Deposited data
Bulk mass spectrometry data	PRIDE	PXD052897
Experimental models: Cell lines
HEK293T	ATCC	Cat# CRL-3216
TV cells	McEwan et al.13	N/A
TVA cells	This paper	N/A
BHK cells	ATCC	Cat# [C-13]-CCL-10
Experimental models: Organisms/strains
Thy1-hTau.P301S mice (CBA.C57BL/6)	M. Goedert laboratory Allen et al.30	Mouse strain: Tg2541
Recombinant DNA
pUCmini-iCAP-PHP.eB	Addgene	Cat# 103005
pAAV-CAG-GFP	Addgene	Cat# 37825
pAdDeltaF6	Addgene	Cat# 112867
pMDG2	Addgene	Cat# 12259
pCRV GagPol	Mallery et al.47	N/A
pSMPPv2-Tau-RING	This paper	N/A
pSMPP-Tau-mCherry	This paper	N/A
pSMPPv2-Tau-mCherry-RING	This paper	N/A
pSMPPv2-Nanobody-mCherry-RING	This paper	N/A
pSMPPv2-Tau-RING (M72E/I18R)	This paper	N/A
pOPTG-Tau-RING	This paper	N/A
pOPTG-Tau-RING (M72E/I18R)	This paper	N/A
AAV 9P31-hSyn-Venus-P2A-Tau-RING	This paper	N/A
AAV 9P31-hSyn-Venus-P2A-Tau-RING I18R/M72E	This paper	N/A
AAV PHP.eB-CAG-Venus	This paper	N/A
AAV PHP.eB-CAG-Venus-P2A-Tau-RING	This paper	N/A
Software and algorithms
DeepLabCut	Mathis et al.33	https://github.com/DeepLabCut
ImageJ	Schindelin et al.48	https://fiji.sc
BioRender	BioRender	https://biorender.com
Prism 10	Graphpad	https://www.graphpad.com
Other
HisTrap FF	GE Healthcare	Cat# 17-5255-01
HisTrap HP	GE Healthcare	Cat# 17-5248-01
HiLoad 16/600 Superdex 200	GE Healthcare	Cat# 28-9893-35
Amicon Ultra-15 concentrators	Merck Millipore	Cat# UFC901024
Amicon Ultra-100 concentrators	Merck Millipore	Cat# UFC910008
Lipofectmine 2000	ThermoFisher	Cat# 11-668-027
OptiMEM	Gibco	Cat# 31985062
DMEM	ThermoFisher	Cat# 11995065
MES Buffer	ThermoFisher	Cat# B0002
MOPS Buffer	ThermoFisher	Cat# J62847-AP
NuPAGE LDS sample buffer	Invitrogen	Cat# NP0008
4X NuPAGE BisTris gel	Invitrogen	Cat# NP0323BOX
FuGENE6	Promega	Cat# E2691
ECL substrate	Merck	Cat# WBKLS0500
Precision Plus Protein Kaleidoscope Ladder	BioRad	Cat# 1610395
PVDF membrane	BioRad	Cat# 1704272
CLARIOstar	BMG Labtech	CLARIOstar
NuPAGE Bis-Tris gel	Invitrogen	Cat# NP0323BOX
Protein kaleidoscope Ladder	BioRad	Cat# 1610395
Prolong Diamond Antifade Mountant	ThermoFisher	Cat# P36961
Glass coverslips	ThermoFisher	Cat# 18X18-1
Carbon Film Supported Copper Square Mesh	Merck	Cat# TEM-CF400-CU-TH
OCT	Sakura	Cat# 94-4583
Glycerol	ThermoFisher	Cat# 15514029
Ethylene Glycol	ThermoFisher	Cat# 29810
Iodixanol	Sigma	Cat# D1556-250
Benzonase	Sigma	Cat# E1014-25KU
Phenol Red	Sigma	Cat# P0290
QIAGEN Plasmid Mini Kit	QIAGEN	Cat# 12123
QIAGEN Plasmid Midi Kit	QIAGEN	Cat# 12143
QIAGEN Plasmid Maxi Kit	QIAGEN	Cat# 12162
PEG8000	VWR	Cat# 71003-444
PEI	Generon	Cat# 24765-1
Optiseal Beckman tubes	ThermoFisher	Cat# 362183
Beckman 1.5 ml Polypropylene Tubes	Beckman Coulter	Cat# 356094
Goat Serum	ThermoFisher	Cat# 16210064
Fetal Bovine Serum	ThermoFisher	Cat# A5670701
Horse Serum	Invitrogen	Cat# 26050070
Paraformaldehyde	ThermoFisher	Cat# 047392.9M
Poly-D-Lysine	Invitrogen	Cat# A3890401
Poly-L-Lysine	RnD Systems	Cat# 3438-100-01
Neurobasal Plus	Gibco	Cat# A3582901
B-27 plus 50x supplement	Gibco	Cat# A35828-01
100x Glutamax	Invitrogen	Cat# 35050038
1% DNAse	Sigma	Cat# DN25-100MG
Hibernate-A	ThermoFisher	Cat# A1247501
Penicillin/Streptomycin	Invitrogen	Cat# 15140122
Heparin	Sigma	Cat# H0878
DTT	Merck	Cat# 10197777001
Thioflavin S	Sigma	Cat# T1892
Halt Protease and Phosphatase inhibitor	ThermoFisher	Cat# 78440