title: Rab5 and its effector FHF contribute to neuronal polarity through dynein-dependent retrieval of somatodendritic proteins from the axon.
abstract: An open question in cell biology is how the general intracellular transport machinery is adapted to perform specialized functions in polarized cells such as neurons. Here we illustrate this adaptation by elucidating a role for the ubiquitous small GTPase Ras-related protein in brain 5 (Rab5) in neuronal polarity. We show that inactivation or depletion of Rab5 in rat hippocampal neurons abrogates the somatodendritic polarity of the transferrin receptor and several glutamate receptor types, resulting in their appearance in the axon. This loss of polarity is not caused primarily by increased transport from the soma to the axon but rather by decreased retrieval from the axon to the soma. Retrieval is also dependent on the Rab5 effector Fused Toes (FTS)-Hook-FTS and Hook-interacting protein (FHIP) (FHF) complex, which interacts with the minus-end-directed microtubule motor dynein and its activator dynactin to drive a population of axonal retrograde carriers containing somatodendritic proteins toward the soma. These findings emphasize the importance of both biosynthetic sorting and axonal retrieval for the polarized distribution of somatodendritic receptors at steady state.
authors: Cell Biology and Neurobiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
authors: Xiaoli
authors: X
authors: Guo
authors: Cell Biology and Neurobiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
authors: Ginny G
authors: GG
authors: Farías
authors: Cell Biology and Neurobiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
authors: Rafael
authors: R
authors: Mattera
authors: Cell Biology and Neurobiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 bonifacinoj@helix.nih.gov.
authors: Juan S
authors: JS
authors: Bonifacino
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D016764:Cell Polarity / Q000235:genetics; D000072159:Dynactin Complex / Q000235:genetics / Q000378:metabolism; D004398:Dyneins / Q000737:chemistry / Q000378:metabolism; D011992:Endosomes / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D021381:Protein Transport; D051381:Rats; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000072159:Dynactin Complex; D004398:Dyneins; D020696:rab5 GTP-Binding Proteins
keywords: FHF complex; Rab5; dynein; neuronal polarity; retrograde transport