RGD Reference Report - Rear polarization of the microtubule-organizing center in neointimal smooth muscle cells depends on PKCalpha, ARPC5, and RHAMM. - Rat Genome Database

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Rear polarization of the microtubule-organizing center in neointimal smooth muscle cells depends on PKCalpha, ARPC5, and RHAMM.

Authors: Silverman-Gavrila, R  Silverman-Gavrila, L  Hou, G  Zhang, M  Charlton, M  Bendeck, MP 
Citation: Silverman-Gavrila R, etal., Am J Pathol. 2011 Feb;178(2):895-910. doi: 10.1016/j.ajpath.2010.10.001.
RGD ID: 11049483
Pubmed: PMID:21281821   (View Abstract at PubMed)
PMCID: PMC3128507   (View Article at PubMed Central)
DOI: DOI:10.1016/j.ajpath.2010.10.001   (Journal Full-text)

Directed migration of smooth muscle cells (SMCs) from the media to the intima in arteries occurs during atherosclerotic plaque formation and during restenosis after angioplasty or stent application. The polarized orientation of the microtubule-organizing center (MTOC) is a key determinant of this process, and we therefore investigated factors that regulate MTOC polarity in vascular SMCs. SMCs migrating in vivo from the medial to the intimal layer of the rat carotid artery following balloon catheter injury were rear polarized, with the MTOC located posterior of the nucleus. In tissue culture, migrating neointimal cells maintained rear polarization, whereas medial cells were front polarized. Using phosphoproteomic screening and mass spectrometry, we identified ARPC5 and RHAMM as protein kinase C (PKC)-phosphorylated proteins associated with rear polarization of the MTOC in neointimal SMCs. RNA silencing of ARPC5 and RHAMM, PKC inhibition, and transfection with a mutated nonphosphorylatable ARPC5 showed that these proteins regulate rear polarization by organizing the actin and microtubule cytoskeletons in neointimal SMCs. Both ARPC5 and RHAMM, in addition to PKC, were required for migration of neointimal SMCs.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Arpc5Ratactin filament network formation  IMP  RGD 
Arpc5Ratlamellipodium organization  IMP  RGD 
Arpc5Ratmaintenance of cell polarity  IMP  RGD 
Arpc5Ratmicrotubule organizing center localization  IMP  RGD 
Arpc5Ratsmooth muscle cell migration  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Arpc5  (actin related protein 2/3 complex, subunit 5)


Additional Information