关键词:
STARD1
Cholesterol trafficking
Fetal Leydig cells
Smoothened
GLI transcription
PKA phosphorylation
Cilium segregation
摘要:
STARD1 stimulates cholesterol transfer to mitochondrial CYP11A1 for conversion to pregnenolone. A cholesterol-binding START domain is guided by an N-terminal domain in a cell selective manner. Fetal and adult Leydig cells (FLC, ALC) show distinct Stard1 regulation. sm- FISH microscopy, which resolves individual molecules of Stard1 mRNA, shows uniformly high basal expression in each FLC. In ALC, in vivo, and cultured MA-10 cells, basal Stard1 expression is minimal. PKA activates loci asynchronously, with delayed splicing/export of 3.5 kb mRNA to mitochondria. After 60 min, ALC transition to an integrated mRNA delivery to mitochondria that is seen in FLC. Sertoli cells cooperate in Stard1 stimulation in FLC by delivering DHH to the primary cilium. There PTCH, SMO and cholesterol cooperate to release GLI3 to activate the Stard1 locus, probably by directing histone changes. ALC lack cilia. PKA then primes locus activation. FLC and ALC share similar SIK/CRTC/CREB regulation characterized for adrenal cells.