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.
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.
Ichiro Ohbayashi
Ken
K
The Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Japan.
Tanaka
Kiyoko
K
Kitajima
Kenji
K
Tamura
Kazuhiro
K
Hara
Takahiko
T
D000818:Animals; D015820:Cadherins / Q000235:genetics*; D002478:Cells, Cultured; D056742:Cyclin D2 / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D039001:Integrin alpha Chains / Q000235:genetics*; D008297:Male; D051379:Mice; D041681:NIH 3T3 Cells; D013090:Spermatocytes / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*
C518363:CMG-1 protein, mouse; D015820:Cadherins; C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D003598:Cytoskeletal Proteins; D039001:Integrin alpha Chains