Small GTPase RhoG is a key regulator for neurite outgrowth in PC12 cells

被引:118
作者
Katoh, H [1 ]
Yasui, H [1 ]
Yamaguchi, Y [1 ]
Aoki, J [1 ]
Fujita, H [1 ]
Mori, K [1 ]
Negishi, M [1 ]
机构
[1] Kyoto Univ, Mol Neurobiol Lab, Grad Sch Biostudies, Sakyo Ku, Kyoto 6068502, Japan
关键词
D O I
10.1128/MCB.20.19.7378-7387.2000
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The Rho family of small GTPases has been implicated in cytoskeletal reorganization and subsequent morphological changes in various cell types. Among them, Rac and Cdc42 have been shown to be involved in neurite outgrowth in neuronal cells. In this study, we examined the role of RhoG, another member of Rho family GTPases, in nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. Expression of wild-type RhoG in PC12 cells induced neurite outgrowth in the absence of NGF, and the morphology of wild-type RhoG-expressing cells was similar to that of NGF-differentiated cells. Constitutively active RhoG-transfected cells extended short neurites but developed large lamellipodial or filopodial structures at the tips of neurites. RhoG-induced neurite outgrowth was inhibited by coexpression with dominant-negative Rac1 or Cdc42. In addition expression of constitutively active RhoG elevated endogenous Rac1 and Cdc42 activities. We also found that the NGF-induced neurite outgrowth was enhanced by expression of wild-type RhoG whereas expression of dominant-negative RhoG suppressed the neurite outgrow th. Furthermore, constitutively active pas-induced neurite outgrowth was also suppressed by dominant-negative RhoG. Taken together, these results suggest that RhoG is a key regulator in NGF-induced neurite outgrowth, acting downstream of Ras and upstream of Rac1 and Cdc42 in PC12 cells.
引用
收藏
页码:7378 / 7387
页数:10
相关论文
共 53 条
[1]   Overexpression of a neural-specific Rho family GTPase, cRac1B, selectively induces enhanced neuritogenesis and neurite branching in primary neurons [J].
Albertinazzi, C ;
Gilardelli, D ;
Paris, S ;
Longhi, R ;
de Curtis, I .
JOURNAL OF CELL BIOLOGY, 1998, 142 (03) :815-825
[2]   MICROINJECTION OF THE RAS ONCOGENE PROTEIN INTO PC12 CELLS INDUCES MORPHOLOGICAL-DIFFERENTIATION [J].
BARSAGI, D ;
FERAMISCO, JR .
CELL, 1985, 42 (03) :841-848
[3]   Characterization of Rac and Cdc42 activation in chemoattractant-stimulated human neutrophils using a novel assay for active GTPases [J].
Benard, V ;
Bohl, BP ;
Bokoch, GM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (19) :13198-13204
[4]  
Blangy A, 2000, J CELL SCI, V113, P729
[5]   Regulatory and signaling properties of the Vav family [J].
Bustelo, XR .
MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (05) :1461-1477
[6]   Oxidation of NO mediated by water-soluble iron porphyrin [J].
Chen, JY ;
Ikeda, O ;
Hatasa, T ;
Kitajima, A ;
Miyake, M ;
Yamatodani, A .
ELECTROCHEMISTRY COMMUNICATIONS, 1999, 1 (07) :274-277
[7]   ACTIVATION OF MAP KINASE KINASE IS NECESSARY AND SUFFICIENT FOR PC12 DIFFERENTIATION AND FOR TRANSFORMATION OF NIH 3T3 CELLS [J].
COWLEY, S ;
PATERSON, H ;
KEMP, P ;
MARSHALL, CJ .
CELL, 1994, 77 (06) :841-852
[8]   Membrane targeting of p21-activated kinase 1 (PAK1) induces neurite outgrowth from PC12 cells [J].
Daniels, RH ;
Hall, PS ;
Bokoch, GM .
EMBO JOURNAL, 1998, 17 (03) :754-764
[9]   The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has separate rac-specific and rho-specific guanine nucleotide exchange factor domains [J].
Debant, A ;
SerraPages, C ;
Seipel, K ;
OBrien, S ;
Tang, M ;
Park, SH ;
Streuli, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (11) :5466-5471
[10]   Ras signalling and apoptosis [J].
Downward, J .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 1998, 8 (01) :49-54