Caldesmon phosphorylation in actin cytoskeletal remodeling

Chi Ming Hai, Zhizhan Gu

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Caldesmon is an actin-binding protein that is capable of stabilizing actin filaments against actin-severing proteins, inhibiting actomyosin ATPase activity, and inhibiting Arp2/3-mediated actin polymerization in vitro. Caldesmon is a substrate of cdc2 kinase and Erk1/2 MAPK, and phosphorylation by either of these kinases reverses the inhibitory effects of caldesmon. Cdc2-mediated caldesmon phosphorylation and the resulting dissociation of caldesmon from actin filaments are essential for M-phase progression during mitosis. Cells overexpressing the actin-binding carboxyterminal fragment of caldesmon fail to release the fragment completely from actin filaments during mitosis, resulting in a higher frequency of multinucleated cells. PKC-mediated MEK/Erk/caldesmon phosphorylation is an important signaling cascade in the regulation of smooth muscle contraction. Furthermore, PKC activation has been shown to remodel actin stress fibers into F-actin-enriched podosome columns in cultured vascular smooth muscle cells. Podosomes are cytoskeletal adhesion structures associated with the release of metalloproteases and degradation of extracellular matrix during cell invasion. Interestingly, caldesmon is one of the few actin-binding proteins that is associated with podosomes but excluded from focal adhesions. Caldesmon also inhibits the function of gelsolin and Arp2/3 complex that are essential for the formation of podosomes. Thus, caldesmon appears to be well positioned for playing a modulatory role in the formation of podosomes. Defining the roles of actin filament-stabilizing proteins such as caldesmon and tropomyosin in the formation of podosomes should provide a more complete understanding of molecular systems that regulate the remodeling of the actin cytoskeleton in cell transformation and invasion.

Original languageEnglish (US)
Pages (from-to)305-309
Number of pages5
JournalEuropean Journal of Cell Biology
Volume85
Issue number3-4
DOIs
StatePublished - Apr 7 2006
Externally publishedYes

Fingerprint

Calmodulin-Binding Proteins
Actins
Phosphorylation
Actin Cytoskeleton
Microfilament Proteins
Mitosis
MAP Kinase Kinase 2
Actin-Related Protein 2-3 Complex
Gelsolin
Stress Fibers
Tropomyosin
Focal Adhesions
Mitogen-Activated Protein Kinase Kinases
Metalloproteases
Myosins
Muscle Contraction
Vascular Smooth Muscle
Polymerization
Cell Division
Smooth Muscle Myocytes

Keywords

  • Actin filament dynamics
  • Caldesmon
  • Podosomes

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Caldesmon phosphorylation in actin cytoskeletal remodeling. / Hai, Chi Ming; Gu, Zhizhan.

In: European Journal of Cell Biology, Vol. 85, No. 3-4, 07.04.2006, p. 305-309.

Research output: Contribution to journalArticle

Hai, Chi Ming ; Gu, Zhizhan. / Caldesmon phosphorylation in actin cytoskeletal remodeling. In: European Journal of Cell Biology. 2006 ; Vol. 85, No. 3-4. pp. 305-309.
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