RGS6 interacts with SCG10 and promotes neuronal differentiation. Role of the G gamma subunit-like (GGL) domain of RGS6

Zhengyu Liu, Tapan Kumar Chatterjee, Rory A. Fisher

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

RGS proteins comprise a large family of proteins named for their ability to negatively regulate heterotrimeric G protein signaling. RGS6 is a member of the R7 RGS protein subfamily endowed with DEP (disheveled, Egl-10, pleckstrin) and GGL (G-protein gamma subunit-like) domains in addition to the RGS domain present in all RGS proteins. RGS6 exists in multiple splice variant forms with identical RGS domains but possessing complete or incomplete GGL domains and distinct N- and C-terminal domains. Here we report that RGS6 interacts with SCG10, a neuronal growth-associated protein. Using yeast two-hybrid analysis to map protein interaction domains, we identified the GGL domain of RGS6 as the SCG10-interacting region and the stathmin domain of SCG10 as the RGS6-interacting region. Pull-down studies in COS-7 cells expressing SCG10 and RGS6 splice variants revealed that SCG10 co-precipitated RGS6 proteins with complete GGL domains but not those with incomplete GGL domains, and vice versa. Expression of SCG10-interacting forms of RGS6 with SCG10 in PC12 or COS-7 cells resulted in co-localization of both proteins. RGS6 potentiated the ability of SCG10 to disrupt microtubule organization in PC12 and COS-7 cells. Furthermore, expression of SCG10 and RGS6 each enhanced NGF-induced PC12 cell differentiation, and co-expression of SCG10 with RGS6 produced synergistic effects on NGF-induced PC12 differentiation. These effects of RGS6 on microtubules and neuronal differentiation were observed only with RGS6 proteins with complete GGL domains. Mutation of a critical residue required for interaction of RGS proteins with G proteins did not affect the ability of RGS6 to induce neuronal differentiation. These findings identify SCG10 as a binding partner for the GGL domain of RGS6 and provide the first evidence for regulatory effects of an RGS protein on neuronal differentiation. Our results suggest that RGS6 induces neuronal differentiation by a novel mechanism involving interaction of SCG10 with its GGL domain and independent of RGS6 interactions with heterotrimeric G proteins.

Original languageEnglish (US)
Pages (from-to)37832-37839
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number40
DOIs
StatePublished - Oct 4 2002

Fingerprint

RGS Proteins
COS Cells
Heterotrimeric GTP-Binding Proteins
Nerve Growth Factor
Microtubules
GTP-Binding Protein gamma Subunits
Proteins
Stathmin
Protein Interaction Domains and Motifs
PC12 Cells
Nerve Growth Factors
GTP-Binding Proteins
Yeast
Cell Differentiation
Yeasts
Cells
Mutation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

RGS6 interacts with SCG10 and promotes neuronal differentiation. Role of the G gamma subunit-like (GGL) domain of RGS6. / Liu, Zhengyu; Chatterjee, Tapan Kumar; Fisher, Rory A.

In: Journal of Biological Chemistry, Vol. 277, No. 40, 04.10.2002, p. 37832-37839.

Research output: Contribution to journalArticle

Liu, Zhengyu ; Chatterjee, Tapan Kumar ; Fisher, Rory A. / RGS6 interacts with SCG10 and promotes neuronal differentiation. Role of the G gamma subunit-like (GGL) domain of RGS6. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 40. pp. 37832-37839.
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abstract = "RGS proteins comprise a large family of proteins named for their ability to negatively regulate heterotrimeric G protein signaling. RGS6 is a member of the R7 RGS protein subfamily endowed with DEP (disheveled, Egl-10, pleckstrin) and GGL (G-protein gamma subunit-like) domains in addition to the RGS domain present in all RGS proteins. RGS6 exists in multiple splice variant forms with identical RGS domains but possessing complete or incomplete GGL domains and distinct N- and C-terminal domains. Here we report that RGS6 interacts with SCG10, a neuronal growth-associated protein. Using yeast two-hybrid analysis to map protein interaction domains, we identified the GGL domain of RGS6 as the SCG10-interacting region and the stathmin domain of SCG10 as the RGS6-interacting region. Pull-down studies in COS-7 cells expressing SCG10 and RGS6 splice variants revealed that SCG10 co-precipitated RGS6 proteins with complete GGL domains but not those with incomplete GGL domains, and vice versa. Expression of SCG10-interacting forms of RGS6 with SCG10 in PC12 or COS-7 cells resulted in co-localization of both proteins. RGS6 potentiated the ability of SCG10 to disrupt microtubule organization in PC12 and COS-7 cells. Furthermore, expression of SCG10 and RGS6 each enhanced NGF-induced PC12 cell differentiation, and co-expression of SCG10 with RGS6 produced synergistic effects on NGF-induced PC12 differentiation. These effects of RGS6 on microtubules and neuronal differentiation were observed only with RGS6 proteins with complete GGL domains. Mutation of a critical residue required for interaction of RGS proteins with G proteins did not affect the ability of RGS6 to induce neuronal differentiation. These findings identify SCG10 as a binding partner for the GGL domain of RGS6 and provide the first evidence for regulatory effects of an RGS protein on neuronal differentiation. Our results suggest that RGS6 induces neuronal differentiation by a novel mechanism involving interaction of SCG10 with its GGL domain and independent of RGS6 interactions with heterotrimeric G proteins.",
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