The role of NADRIN, a Rho GTPase-activating protein, in the morphological differentiation of astrocytes.
Reorganization of the actin cytoskeleton caused by inactivation of the Rho GTPase RhoA is critical for the morphological differentiation of astrocytes into process-bearing stellate cells. The molecular mechanisms underlying the RhoA inactivation and, in particular, the factors that inactivate RhoA, remain to be elucidated. We show here that the expression of a GTPase-activating protein (GAP) for Rho GTPases, neuron-associated developmentally regulated protein (NADRIN) also known as RICH and ARHGAP17, was significantly increased in stellate astrocytes and induced expression of NADRIN accelerated the morphological differentiation of cultured astrocytes into stellate cells. A GAP activity-negative mutant or truncated forms of NADRIN failed to induce the stellation. Immunoprecipitation analyses revealed that, in response to inductive signals such as dibutyryl cyclic AMP and epidermal growth factor, NADRIN formed a complex with ezrin-radixin-moesin (ERM) protein by interacting with ERM-binding phosphoprotein 50 via its carboxy-terminal PSD95/DlgA/ZO-1-binding motif. We also showed that NADRIN formed a dimer via the interaction between the amino- and carboxy-terminal domains, which was disrupted in response to the inductive signals. These results suggest that the inductive signals cause the structural change of NADRIN, which allows NADRIN to associate with the ERM protein complex, where it inactivates RhoA and leads to the morphological differentiation of astrocytes.
The Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, 3-18-22 Honkomagome, Tokyo 113-8613, Japan.
Yoko
Y
Kobayashi
Ayako
A
Harada
Birei
B
Furuta
Hiroaki
H
Asou
Utako
U
Kato
Masato
M
Umeda
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D004268:DNA-Binding Proteins / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009154:Mutation; D010750:Phosphoproteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
C504467:Arhgap17 protein, mouse; D004268:DNA-Binding Proteins; C513242:Etv5 protein, mouse; D020690:GTPase-Activating Proteins; D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; D014157:Transcription Factors; C093376:sodium-hydrogen exchanger regulatory factor