Unphosphorylated MARCKS is involved in neurite initiation induced by insulin-like growth factor-I in SH-SY5Y cells

Mitsuya Shiraishi, Atsuhiro Tanabe, Naoaki Saito, Yasuharu Sasaki

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Myristoylated alanine-rich C kinase substrate (MARCKS) has been suggested to be involved in various aspects of neuronal cell differentiation, including neurite outgrowth. However, the precise mechanisms by which MARCKS phosphorylation is regulated, and how MARCKS contributes to neurite outgrowth, are poorly understood. Here, we found that treatment of SH-SY5Y cells with insulin-like growth factor-I (IGF-I) induced a rapid and transient decrease in the level of phosphorylated MARCKS (P-MARCKS) to below the basal level. The decrease in P-MARCKS induced by IGF-I was blocked by pretreatment of cells with phosphoinositide 3-kinase (PI3K) inhibitors, LY294002 and wortmannin. A decrease in P-MARCKS was also observed in cells treated with a Rho-dependent kinase (ROCK) inhibitor, Y27632. Furthermore, IGF-I induced transient inactivation of RhoA, an upstream effector of ROCK. We showed that MARCKS was translocated to the membrane and colocalized with F-actin at the lamellipodia and the tips of neurites in the cells stimulated with IGF-I. Finally, overexpression of wild-type MARCKS or an unphosphorylatable mutant of MARCKS enhanced the number of neurite-bearing cells relative to vector-transfected cells. Taken together, these findings suggest that unphosphorylated MARCKS is involved in neurite initiation, and highlight the important role played by MARCKS in organization of the actin cytoskeleton.

Original languageEnglish
Pages (from-to)1029-1038
Number of pages10
JournalJournal of Cellular Physiology
Volume209
Issue number3
DOIs
Publication statusPublished - 2006 Dec
Externally publishedYes

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Insulin-Like Growth Factor I
Actins
Bearings (structural)
Phosphotransferases
myristoylated alanine-rich C kinase substrate
Phosphorylation
Phosphatidylinositols
Cells
Membranes

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Unphosphorylated MARCKS is involved in neurite initiation induced by insulin-like growth factor-I in SH-SY5Y cells. / Shiraishi, Mitsuya; Tanabe, Atsuhiro; Saito, Naoaki; Sasaki, Yasuharu.

In: Journal of Cellular Physiology, Vol. 209, No. 3, 12.2006, p. 1029-1038.

Research output: Contribution to journalArticle

Shiraishi, Mitsuya ; Tanabe, Atsuhiro ; Saito, Naoaki ; Sasaki, Yasuharu. / Unphosphorylated MARCKS is involved in neurite initiation induced by insulin-like growth factor-I in SH-SY5Y cells. In: Journal of Cellular Physiology. 2006 ; Vol. 209, No. 3. pp. 1029-1038.
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