Review Article

Reorganization of the Vimentin Network in Smooth Muscle

[+] Author and Article Information
Dale D. Tang

Department of Molecular and
Cellular Physiology,
Albany Medical College,
47 New Scotland Avenue, MC-8,
Albany, NY 12118
e-mail: tangd@amc.edu

Guoning Liao, Brennan D. Gerlach

Department of Molecular and
Cellular Physiology,
Albany Medical College,
47 New Scotland Avenue, MC-8,
Albany, NY 12118

1Corresponding author.

Manuscript received August 24, 2018; final manuscript received September 21, 2018; published online January 18, 2019. Assoc. Editor: Chun Seow.

ASME J of Medical Diagnostics 2(1), 010801 (Jan 18, 2019) (5 pages) Paper No: JESMDT-18-1037; doi: 10.1115/1.4042313 History: Received August 24, 2018; Revised September 21, 2018

Vimentin intermediate filaments (IFs) link to desmosomes (intercellular junctions) on the membrane and dense bodies in the cytoplasm, which provides a structural base for intercellular and intracellular force transmission in smooth muscle. There is evidence to suggest that the vimentin framework plays an important role in mediating smooth muscle mechanical properties such as tension and contractile responses. Contractile activation induces vimentin phosphorylation at Ser-56 and vimentin network reorientation, facilitating contractile force transmission among and within smooth muscle cells. p21-activated kinase 1 and polo-like kinase 1 catalyze vimentin phosphorylation at Ser-56, whereas type 1 protein phosphatase dephosphorylates vimentin at this residue. Vimentin filaments are also involved in other cell functions including migration and nuclear positioning. This review recapitulates our current knowledge how the vimentin network modulates mechanical and biological properties of smooth muscle.

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Grahic Jump Location
Fig. 1

Schematic illustration of intermediate filaments and the desmosome in smooth muscle. Vimentin intermediate filaments connect with the cytoplasmic domain of desmocollin and desmoglein via the linker proteins such as plakoglobin, plakophilin, and desmoplakin. The extracellular domains of desmocollin and desmoglein interact with their counterparts in adjacent cells to form the intercellular junction. Another end of vimentin filaments links to the cytoplasmic dense bodies to which actin filaments also attach. Desmin intermediate filaments are positioned in the peripheral of airway smooth muscle cells facilitating the connection of vimentin filaments to the desmosome.

Grahic Jump Location
Fig. 2

Regulation of vimentin phosphorylation at Ser-56 in smooth muscle. Besides myosin activation, contractile agonists activate NAD(P)H oxidase that promotes ROS generation. Increased ROS inhibits Cdc42GAP activity, and triggers the small GTPase that turns on PAK1. Activated PAK1 catalyzes vimentin phosphorylation at Ser-56, which induces vimentin network rearrangement. Phosphorylated vimentin also releases p130CAS, which promotes actin polymerization. In addition, vimentin phosphorylation is mediated by the SLK-Plk1 pathway, whereas its dephosphorylation is regulated by PP1. Vimentin network reorganization, myosin activation, and actin polymerization facilitate smooth muscle contraction.



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