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Significance Ras-related proteins in brain (Rab) GTPases are general regulators of intracellular traffic in eukaryotic cells, but their specialized roles in neurons are poorly understood. Here we report that Rab5 contributes to the somatodendritic polarity of various surface receptors by mediating their retrieval from the axon. This retrieval is dependent on the Rab5 effector Fused Toes (FTS)–Hook–FTS and Hook-interacting protein (FHIP) (FHF), which in turn interacts with the minus-end–directed microtubule motor dynein–dynactin to drive retrograde transport of receptor-containing carriers from the axon to the soma. These findings reveal a mechanism for coupling axonal retrograde carriers to dynein–dynactin and demonstrate that the somatodendritic polarity of various receptors results from a combination of biosynthetic sorting, the barrier function of the axon initial segment, and retrieval from the axon.

Rab5 and its effector FHF contribute to neuronal polarity through dynein-dependent retrieval of somatodendritic proteins from the axon