StarD7 deficiency hinders cell motility through p-ERK1/2/Cx43 reduction

PLoS One. 2022 Dec 30;17(12):e0279912. doi: 10.1371/journal.pone.0279912. eCollection 2022.

Abstract

StarD7 belongs to START protein family involved in lipid traffic, metabolism, and signaling events. Its precursor, StarD7.I which is important for mitochondrial homeostasis, is processed to the StarD7.II isoform that lacks the mitochondrial targeting sequence and is mainly released to the cytosol. StarD7 knockdown interferes with cell migration by an unknown mechanism. Here, we demonstrate that StarD7 silencing decreased connexin 43 (Cx43), integrin β1, and p-ERK1/2 expression in the non-tumoral migratory HTR-8/SVneo cells. StarD7-deficient cells exhibited Golgi disruption and reduced competence to reorient the microtubule-organizing center. The migratory capacity of StarD7-silenced cells was reestablished when Cx43 level was resettled, while p-ERK1/2 expression remained low. Importantly, ectopic expression of the StarD7.II isoform not only restored cell migration but also ERK1/2, Cx43, and integrin β1 expression. Thus, StarD7 is implicated in cell migration through an ERK1/2/Cx43 dependent mechanism but independent of the StarD7.I function in the mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins* / metabolism
  • Cell Movement / genetics
  • Connexin 43* / genetics
  • Connexin 43* / metabolism
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism
  • MAP Kinase Signaling System
  • Protein Isoforms / metabolism

Substances

  • Carrier Proteins
  • Connexin 43
  • Integrin beta1
  • Protein Isoforms

Grants and funding

JF-M Received PICT 2020-00201 from FONCYT and 33620180100028CB from SECyT-UNC. SG-R Received PICT 2017-0899 from FONCYT SG-R Received PICT 2014-0806 from FONCYT ACR Received PICT 2019-00478 from FONCYT GMP-D Received PICT 2015-1781 from FONCYT Agencia Nacional de Promoción Científica y Tecnológica (FONCYT). URL: https://www.argentina.gob.ar/ciencia/agencia/fondo-para-la-investigacion-cientifica-y-tecnologica-foncyt Secretaría de Ciencia y Técnica de la Universidad Nacional de Córdoba (SECyT-UNC). URL: https://www.unc.edu.ar/ciencia-y-tecnología The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.