The integration of autophagy and cellular trafficking pathways via RAB GAPs

Figures & data

Figure 1. Schematic representation of RAB GAPs established to function in macroautophagy. TBC1D5, TBC1D14, and RAB3GAP1/2 function during autophagosome formation, and TBC1D2 and TBC1D25 support autophagosome-lysosome fusion. The TBC domain is depicted by dark purple globules. Note that this domain is missing in the heterodimeric RAB3GAP complex.

Table 1. Summary of macroautophagy-associated RAB GAPs.

RAB GAP	Substrate RAB GTPases	Nonautophagic function(s)	Association with Macroautophagy
TBC1D1	RAB2A, RAB8A, RAB8B, RAB10, RAB14	SLCA4/GLUT4 trafficking,^31 glucose metabolism^32	binds to Atg8 family members^15
TBC1D2 (Armus, PARIS1)	RAB7	CDH1/E-cadherin degradation^33	binds to Atg8 family members;^15 modulates autophagosome-lysosome fusion^18
TBC1D2B	RAB22A, RAB22B	ND	binds to Atg8 family members^15
TBC1D4 (AS160)	RAB2A, RAB8A, RAB10, RAB14	SLC2A4/GLUT4 trafficking, insulin sensitivity^34,35	OE inhibits autophagy^14
TBC1D5	RAB7	endocytic trafficking^17,36	binds to Atg8 family members;^15 regulates ATG9 trafficking and autophagosome formation^15,17
TBC1D7	RAB17	primary cilium formation;^37 influences MTOR activity^38	OE inhibits autophagy;^14 binds to Atg8 family members;^15 influences MTOR activity^38
TBC1D9	ND	ND	OE inhibits autophagy;^14 binds to Atg8 family members^15
TBC1D9B	RAB11A	basolateral-to-apical transcytosis^39	OE inhibits autophagy^14
TBC1D10A (EPI64)	RAB27A, RAB27B, RAB35, RAB8A	melanosome transport;^40 endocytic trafficking and microvillus structure;^41 exosome secretion^42	OE inhibits autophagy;^14 binds to Atg8 family members^15
TBC1D10B (EPI64B)	RAB3A, RAB22A, RAB27A, RAB27B, RAB31, RAB35	exosome secretion;^42 regulation of exocytosis^43	OE inhibits autophagy;^14 binds to Atg8 family members^15
TBC1D10C (EPI64C, Carabin)	RAB35	T cell receptor recycling, immunological synapse formation;^44 exosome secretion;^42 PPP3/calcineurin, NFAT, RRAS, MAPK/ERK, and CAMK2 signaling^45	OE inhibits autophagy^14
TBC1D14	ND	endocytic trafficking^14	OE inhibits autophagy;^14 regulates autophagosome formation^14
TBC1D16	RAB4A, RAB5C	EGFR recycling from endosomes^46	OE inhibits autophagy;^14 binds to Atg8 family members^15
TBC1D17	RAB21, RAB8	endocytic trafficking, interacts with OPTN^47	OE inhibits autophagy;^14 binds to Atg8 family members^15
TBC1D25 (OATL1)	RAB2A, RAB13, RAB34, RAB33A, RAB33B	ND	binds to Atg8 family members;^13,15 regulates autophagosome formation^13
RABGAP1 (TBC1D11, GAPCenA)	RAB2, RAB4, RAB6A, RAB6B, RAB11, RAB36	microtubule and Golgi dynamics, metaphase/anaphase transition^48,49	binds to Atg8 family members^15
RABGAP1L (TBC1D18, HHL)	RAB22A, RAB34, RAB39B	ND	binds to Atg8 family members^15
SGSM2 (RUTBC1)	RAB9A, RAB32, RAB33B,	ND	OE inhibits autophagy^14
RAB3GAP1/2	GAP: RAB3A-D,^50 GEF: RAB18^23	neurotransmitter release;^20 LMAN1 trafficking;^25 CLDN1 exocytosis;^26 maintenance of ER structure^23	regulates autophagosome formation^22

OE, overexpression

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