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Scribble controls NGF-mediated neurite outgrowth in PC12 cells
Södertörn University, School of Natural Sciences, Technology and Environmental Studies, Biology. Dalhousie University.
Södertörn University, School of Natural Sciences, Technology and Environmental Studies, Biology.
Södertörn University, School of Natural Sciences, Technology and Environmental Studies, Biology.
Södertörn University, School of Natural Sciences, Technology and Environmental Studies, Biology. Örebro university.
2013 (English)In: European Journal of Cell Biology, ISSN 0171-9335, E-ISSN 1618-1298, Vol. 92, no 6-7, 213-221 p.Article in journal (Refereed) Published
Abstract [en]

Neurite outgrowth is mediated by dynamic changes of the cytoskeleton and is largely controlled by Rho GTPases and their regulators. Here, we show that the polarity protein Scribble controls PC12 cell neurite outgrowth in response to nerve growth factor. Scribble knockdown decreases neurite numbers and increases neurite length. This effect is linked to TrkA the cognate receptor for NGF as pharmacological inhibition of phosphorylated TrkA (pTrkA) reduces Scribble expression. Moreover, Scribble forms a complex with the MAPK components ERK1/2 in a growth factor dependent manner. In RNAi experiments where Scribble expression is efficiently depleted sustained ERK1/2 phosphorylation is reduced. Conversely, siRNA with intermediate Scribble silencing efficiency fails to match this effect indicating that ERK1/2 activation depends on basic Scribble protein levels. Finally, Scribble translocates to the plasma membrane in response to growth factor where it complexes with HRas and Rac1 suggesting that the phenotype activated by loss of Scribble may be a result of altered GTPase activity. Together, these results demonstrate a novel role for Scribble in neurite outgrowth of PC12 cells.

Place, publisher, year, edition, pages
2013. Vol. 92, no 6-7, 213-221 p.
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:sh:diva-19833DOI: 10.1016/j.ejcb.2013.07.002ISI: 000324971200003PubMedID: 23973368Scopus ID: 2-s2.0-84883244028OAI: oai:DiVA.org:sh-19833DiVA: diva2:651890
Funder
The Foundation for Baltic and East European StudiesKnowledge Foundation
Note

Funding agency: Carl Tryggers foundation

Available from: 2013-09-27 Created: 2013-09-27 Last updated: 2016-11-14Bibliographically approved

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CiteExportLink to record
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Citation style
  • apa
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