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A Rab1 interactome illuminates its dual role in autophagy and membrane trafficking

ABSTRACT: The small GTPase Rab1 is found in all eukaryotes and acts in both ER-to-Golgi transport and autophagy. Several Rab1 effectors and regulators have been identified, but the mechanism by which Rab1 orchestrates these distinct processes remains incompletely understood. We apply MitoID, a proximity biotinylation approach, to expand the interactome of human Rab1A and Rab1B. We identify new interactors amongst known membrane traffic and autophagy machinery, as well as previously uncharacterised proteins. One striking set of interactors are the cargo receptors for selective autophagy, indicating a broader role for Rab1 in autophagy than previously supposed. Two cargo receptor interactions are validated in vitro, with the Rab1 binding site in the cargo receptor optineurin being required for mitophagy in vivo. We also find an interaction between Rab1 and the dynein adaptor FHIP2A that can only be detected in the presence of membranes. This explains recruitment of dynein to the ER-Golgi-intermediate compartment and demonstrates that conventional methods can miss a subset of effectors of small GTPases.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Catarina Franco

LAB HEAD: Sean Munro

PROVIDER: PXD065220 | Pride | 2025-12-18

REPOSITORIES: Pride

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			Action	DRS
	1390176892_Alex_10_DIA_SCX.raw	Raw
	1390176892_Alex_11_DIA_SCX.raw	Raw
	1390176892_Alex_12_DIA_SCX.raw	Raw
	1390176892_Alex_13_DIA_SCX.raw	Raw
	1390176892_Alex_14_DIA_SCX.raw	Raw

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