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LIN7 regulates the filopodia and neurite promoting activity of IRSp53
- Source :
- Journal of Cell Science
- Publication Year :
- 2012
- Publisher :
- The Company of Biologists, 2012.
-
Abstract
- The insulin receptor substrate protein of 53 kDa (IRSp53) is crucially involved in the formation of filopodia and neurites through mechanisms that have only partially been clarified. We have investigated the role of the small scaffold protein LIN7, which interacts with IRSp53. We found that formation of actin-filled protrusions in neuronal NSC34 cells and neurites in neuroblastoma N2A cells depends on motifs mediating the LIN7:IRSp53 association, as both the coexpression of LIN7 with IRSp53 or the expression of the L27-IRSp53 chimera (a fusion protein between IRSp53 and the LIN7L27 domain for plasma membrane protein complexes association) prevented actin-deficient protrusions induced by overexpressed IRSp53, and enhanced the formation of actin-filled protrusions. The regulatory role of LIN7 in IRSp53-mediated extension of filopodia in neuronal N2A cells was demonstrated by live-cell imaging experiments. Moreover, LIN7 silencing prevented the extension of filopodia and neurites, induced by ectopic expression of IRSp53 or serum starvation, respectively, in undifferentiated and differentiated N2A cells. The expression of full-length IRSp53 or the LIN7ΔPDZ mutant lacking the domain for association with IRSp53 was unable to restore neuritogenesis in LIN7-silenced cells. Conversely, defective neuritogenesis could be rescued by the expression of RNAi-resistant full-length LIN7 or chimeric L27-IRSp53. Finally, LIN7 silencing prevented the recruitment of IRSp53 in Triton X-100-insoluble complexes, otherwise occurring in differentiated cells. Collectively these data indicate that LIN7 is a novel regulator of IRSp53, and that the association of these proteins is required to promote the formation of actin-dependent filopodia and neurites.
- Subjects :
- Scaffold protein
Neurite
Cell Survival
Octoxynol
Cellular differentiation
Amino Acid Motifs
Vesicular Transport Proteins
Nerve Tissue Proteins
Biology
Cell Line
Mice
03 medical and health sciences
0302 clinical medicine
Neurites
Animals
Humans
Gene silencing
Pseudopodia
030304 developmental biology
2. Zero hunger
0303 health sciences
Membrane Proteins
Cell Differentiation
Cell Biology
Fusion protein
Protein Structure, Tertiary
Cell biology
Protein Transport
Solubility
Cell culture
Ectopic expression
Filopodia
030217 neurology & neurosurgery
Protein Binding
Subjects
Details
- ISSN :
- 14779137 and 00219533
- Database :
- OpenAIRE
- Journal :
- Journal of Cell Science
- Accession number :
- edsair.doi.dedup.....70d85f205a1a9fd173bc3d54b7d06d95