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Rabin8 regulates neurite outgrowth in both GEF activity–dependent and –independent manners

Homma, Yuta, Fukuda, Mitsunori·2016·Molecular Biology of the Cell
DOI 10.1091/mbc.e16-02-0091PMC PMC4927283
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Abstract

Many aspects of membrane-trafficking events are regulated by Rab-family small GTPases. Neurite outgrowth requires massive addition of proteins and lipids to the tips of growing neurites by membrane trafficking, and although several Rabs, including Rab8, Rab10, and Rab11, have been implicated in this process, their regulatory mechanisms during neurite outgrowth are poorly understood. Here, we show that Rabin8, a Rab8-guanine nucleotide exchange factor (GEF), regulates nerve growth factor (NGF)–induced neurite outgrowth of PC12 cells. Knockdown of Rabin8 results in inhibition of neurite outgrowth, whereas overexpression promotes it. We also find that Rab10 is a novel substrate of Rabin8 and that both Rab8 and Rab10 function during neurite outgrowth downstream of Rabin8. Surprisingly, however, a GEF activity–deficient isoform of Rabin8 also promotes neurite outgrowth, indicating the existence of a GEF activity–independent role of Rabin8. The Arf6/Rab8-positive recycling endosomes (Arf6/Rab8-REs) and Rab10/Rab11-positive REs (Rab10/Rab11-REs) in NGF-stimulated PC12 cells are differently distributed. Rabin8 localizes on both RE populations and appears to activate Rab8 and Rab10 there. These localizations and functions of Rabin8 are Rab11 dependent. Thus Rabin8 regulates neurite outgrowth both by coordinating with Rab8, Rab10, and Rab11 and by a GEF activity–independent mechanism.

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  • RAB8 and RAB10 can cooperatively regulate other vesicular trafficking pathways including basolateral sorting, neurite outgrowth, and ciliogenesis.

    “and with previous reports showing that RAB8 and RAB10 can cooperatively regulate other vesicular trafficking pathways including basolateral sorting, neurite outgrowth, and ciliogenesis [42,43,44,45].”

    From Distinct Roles for RAB10 and RAB29 in Pathogenic LRRK2-Mediated Endolysosomal Trafficking Alterations (2020) · cites this paper as [44]

    The Results section (‘Both Rab8 and Rab10 are involved in neurite outgrowth of PC12 cells’; page unavailable) reports that inhibiting either impairs neurite outgrowth, while suggesting they act independently on different recycling endosomes. The Discussion (‘A Rab cascade on REs and its role during neurite outgrowth’; page unavailable) proposes that Rabin8 activates both; it only speculates about a Rab10 cascade in ciliogenesis and does not establish cooperative Rab8–Rab10 regulation of basolateral sorting. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • RAB10 modulates a variety of membrane trafficking events including exocytic polarized targeting and endocytic recycling, and can perform functions partially redundant with RAB8A.

    “RAB10 has been described to modulate a variety of membrane trafficking events including exocytic polarized targeting and endocytic recycling events [41], and can perform functions partially redundant with those of RAB8A [42,43,44,45].”

    From Distinct Roles for RAB10 and RAB29 in Pathogenic LRRK2-Mediated Endolysosomal Trafficking Alterations (2020) · cites this paper as [44]

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Citations

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Metadata

Authors
Homma, Y., & Fukuda, M.
Affiliations
Laboratory of Membrane Trafficking Mechanisms, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aobayama, Aoba-ku, Sendai, Miyagi 980-8578, Japan
Venue
Molecular Biology of the Cell
Publisher
American Society for Cell Biology (ASCB)
Published
2016-07
Volume
27
Issue
13
Pages
2107-2118
ISSN
  • 1059-1524
  • 1939-4586
DOI
10.1091/mbc.e16-02-0091
PMC
PMC4927283
Cited by
84
References
3
Language
en

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