NDLI: Lipid Raft Targeting of the TC10 Amino Terminal Domain Is Responsible for Disruption of Adipocyte Cortical Actin

Content Provider	PubMed Central
Author	Hou, June Chunqiu Pessin, Jeffrey E.
Editor	Keith, Mostov
Copyright Year	2003
Abstract	Overexpression of the Rho family member TC10α, disrupts adipocyte cortical actin structure and inhibits insulin-stimulated GLUT4 translocation when targeted to lipid raft microdomains. This appears to be independent of effecter domain function because overexpression of the wild-type (TC10/WT), constitutively GTP-bound (TC10/Q75L), and constitutively GDP bound (TC10/T31N) all inhibit adipocyte cortical actin structure and GLUT4 translocation. To examine the structural determinants responsible for these effects, we generated a series of chimera proteins between TC10 with that of H-Ras and K-Ras. Chimera containing the 79 (TC10–79/H-Ras), 41 (TC10–41/H-Ras), or 16 (TC10–16/H-Ras) amino acids of the TC10 amino terminal extension fused to H-Ras disrupted cortical actin and inhibited insulin-stimulated GLUT4 translocation. In contrast, the same amino terminal TC10 extensions fused to K-Ras had no significant effect on either GLUT4 translocation or cortical actin structure. Similarly, expression of TC10β was without effect, whereas fusion of the amino terminal 8 amino acid of TC10α onto TC10β resulted in an inhibition of insulin-stimulated GLUT4 translocation. Within the amino terminal extension point mutation analysis demonstrated that both a GAG and GPG sequences when lipid raft targeted was essential for these effects. Furthermore, expression of the amino terminal TC10 deletions ΔNT-TC10/WT or ΔNT-TC10/T31N had no detectable effect on cortical actin organization and did not perturb insulin-stimulated GLUT4 translocation. Surprisingly, however, expression of ΔNT-TC10/Q75L remained fully capable of inhibiting insulin-stimulated GLUT4 translocation without affecting cortical actin. These data demonstrate that inhibitory effect of TC10 overexpression on adipocyte cortical actin organization is due to the specific lipid raft targeting of the unusual TC10 amino terminal extension.
Related Links	http://dx.doi.org/10.1091/mbc.e03-01-0012
Ending Page	3591
Page Count	14
Starting Page	3578
File Format	PDF
ISSN	10591524
Journal	Molecular Biology of the Cell
Issue Number	9
Volume Number	14
Language	English
Publisher	The American Society for Cell Biology
Publisher Date	2003-07-01
Access Restriction	Open
Rights Holder	The American Society for Cell Biology
Subject Keyword	Cell Biology Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology

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