Novel role for the intraflagellar transport protein CMG-1 in regulating the transcription of cyclin-D2, E-cadherin and integrin-alpha family genes in mouse spermatocyte-derived cells

Genes Cells. 2010 Jun;15(7):699-710. doi: 10.1111/j.1365-2443.2010.01414.x. Epub 2010 Jun 2.

Abstract

Capillary morphogenesis gene (CMG)-1 is a mammalian homologue of the intraflagellar transport protein IFT-74/72 of Chlamydomonas. CMG-1 is abundantly expressed in immature stages of male germ-line cells of the adult mouse testis and is required for the expression of cyclin-D2 in GC-2, a mouse premeiotic spermatocyte-derived cell line. In this study, we show that the knockdown of CMG-1 in GC-2 cells leads to down-regulation of E-cadherin, integrin-alpha1, alpha2, alpha10, and alpha11 expression. The ability of the CMG-1-knockdown GC-2 cells to adhere to type-I collagen-coated plates was consequently impaired. Inducible expression of an siRNA-resistant CMG-1 cDNA in these cells rescued the expression of E-cadherin and the integrin-alpha family genes and partially restored adherence to type-I collagen. CMG-1 participates in the transcriptional regulation of cyclin-D2 via a genomic DNA region between -250 and -216 of the mouse cyclin-D2 gene. Closely related sequences were found in the enhancer/promotor regions of E-cadherin and the four integrin-alpha family genes. Based on these data, we propose that CMG-1 serves as a transcriptional regulator of proliferation and adhesion-associated genes in early stage male germ-line cells in the testis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / genetics*
  • Cells, Cultured
  • Cyclin D2 / genetics*
  • Cytoskeletal Proteins / metabolism*
  • Integrin alpha Chains / genetics*
  • Male
  • Mice
  • NIH 3T3 Cells
  • Spermatocytes / metabolism*
  • Transcription, Genetic / genetics*

Substances

  • CMG-1 protein, mouse
  • Cadherins
  • Ccnd2 protein, mouse
  • Cyclin D2
  • Cytoskeletal Proteins
  • Integrin alpha Chains