Protrudin induces neurite formation by directional membrane trafficking.
Guanosine triphosphatases of the Rab family are key regulators of membrane trafficking, with Rab11 playing a specific role in membrane recycling. We identified a mammalian protein, protrudin, that promoted neurite formation through interaction with the guanosine diphosphate (GDP)-bound form of Rab11. Phosphorylation of protrudin by extracellular signal-regulated kinase (ERK) in response to nerve growth factor promoted protrudin association with Rab11-GDP. Down-regulation of protrudin by RNA interference induced membrane extension in all directions and inhibited neurite formation. Thus, protrudin regulates Rab11-dependent membrane recycling to promote the directional membrane trafficking required for neurite formation.
Shirane
Michiko
M
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan.
Nakayama
Keiichi I
KI
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D020932:Nerve Growth Factor / Q000494:pharmacology / Q000502:physiology; D016501:Neurites / Q000502:physiology*; D016716:PC12 Cells; D010766:Phosphorylation; D034622:RNA Interference; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D048049:Extracellular Signal-Regulated MAP Kinases; D006153:Guanosine Diphosphate; D048369:MAP Kinase Kinase 1; D008565:Membrane Proteins; D020932:Nerve Growth Factor; D011993:Recombinant Fusion Proteins; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C513390:ZFYVE27 protein, human; C514782:Zfyve27 protein, rat; C514783:protrudin protein, mouse