Document Detail

Regulation of vesicle transport and cell motility by Golgi-localized Dbs.
MedLine Citation:
PMID:  25483302     Owner:  NLM     Status:  Publisher    
DBS/MCF2L has been recently identified as a risk locus for osteoarthritis. It encodes a guanine nucleotide exchange factor (Dbs) that has been shown to regulate both normal and tumor cell motility. In the current study we have determined that endogenous Dbs is predominantly expressed as 2 isoforms, a 130 kDa form (Dbs-130) that is localized to the Golgi complex, and an 80 kDa form (Dbs-80) that is localized to the endoplasmic reticulum (ER). We have previously described an inhibitor that binds to the RhoGEF domain of Dbs and blocks its transforming activity. Here we show that the inhibitor localizes to the Golgi, where it specifically interacts with Dbs-130. Inhibition of endogenous Dbs-130 activity is associated with reduced levels of activated Cdc42, enlarged Golgi, and resistance to Brefeldin A-mediated Golgi dispersal, suggesting a role for Dbs in vesicle transport. Cells treated with the inhibitor exhibit normal protein transport from the ER to the Golgi, but are defective in transport from the Golgi to the plasma membrane. Inhibition of Dbs-130 in MDA-MB-231 human breast tumor cells, limits motility in both transwell and wound healing assays, but appears to have no effect on the organization of the microtubule cytoskeleton. The reduced motility is associated with a failure to reorient the Golgi toward the leading edge. This is consistent with the Golgi localization, and suggests that the Dbs-130 regulates aspects of the secretory pathway that are required to support cell polarization during directed migration.
Ethan R Fitzpatrick; Tinghui Hu; Bryan T Ciccarelli; Ian P Whitehead
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-5-8
Journal Detail:
Title:  Small GTPases     Volume:  -     ISSN:  2154-1256     ISO Abbreviation:  Small GTPases     Publication Date:  2014 May 
Date Detail:
Created Date:  2014-12-8     Completed Date:  -     Revised Date:  2014-12-9    
Medline Journal Info:
Nlm Unique ID:  101530974     Medline TA:  Small GTPases     Country:  -    
Other Details:
Languages:  ENG     Pagination:  e28570     Citation Subset:  -    
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