RGS2 promotes formation of neurites by stimulating microtubule polymerization.
Regulator of G-protein signaling (RGS) proteins interact with alpha subunits of heterotrimeric G-proteins via the RGS domain and attenuate their activity by accelerating GTPase activity. RGS2, a member of the RGS family, regulates synaptic development via hereto unknown mechanism. In this study, we found that RGS2 directly interacted with tubulin via a short region at the N-terminus: amino acids 41-60. RGS2 enhanced microtubule polymerization in vitro, and the tubulin binding region was necessary and sufficient for this activity. In Vero cells, polymerization of microtubule was stimulated when peptides containing the tubulin binding region were microinjected. Immunocytochemical analysis showed that endogenous RGS2 was localized at the termini of neurites in differentiated PC12 cells. Over-expression of RGS2 enhanced the nerve growth factor-induced neurite outgrowth in PC12 cells, while specific knock-down of endogenous RGS2 suppressed the neurite outgrowth. These findings demonstrate that RGS2 contributes to the neuronal cell differentiation via regulation of microtubule dynamics.
Heo
Kyun
K
Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, South Korea.
Ha
Sang Hoon
SH
Chae
Young Chan
YC
Lee
Sukmook
S
Oh
Yong-Seok
YS
Kim
Yun-Hee
YH
Kim
Sun-Hee
SH
Kim
Jung Hwan
JH
Mizoguchi
Akira
A
Itoh
Tomohiko J
TJ
Kwon
H Moo
HM
Ryu
Sung Ho
SH
Suh
Pann-Ghill
PG
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002522:Chlorocebus aethiops; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics; D016501:Neurites / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D016716:PC12 Cells; D011485:Protein Binding; D020710:RGS Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014162:Transfection / Q000379:methods; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D014709:Vero Cells
D020710:RGS Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D014404:Tubulin; D049452:Green Fluorescent Proteins; D005982:Glutathione Transferase