Distinctive functioning of STARD1 in the fetal Leydig cells compared to adult Leydig and adrenal cells. Impact of Hedgehog signaling via the primary cilium

被引:1
|
作者
Kothandapani, Anbarasi [1 ]
Larsen, Michele Campaigne [2 ]
Lee, Jinwoo [2 ]
Jorgensen, Joan S. [1 ]
Jefcoate, Colin R. [2 ]
机构
[1] Univ Wisconsin, Dept Comparat Biosci, Sch Vet Med, Madison, WI 53706 USA
[2] Univ Wisconsin, Dept Cell & Regenerat Biol, Sch Med & Publ Hlth, 1111 Highland Ave,4459 WIMR 2, Madison, WI 53705 USA
基金
美国国家卫生研究院;
关键词
STARD1; Cholesterol trafficking; Fetal Leydig cells; Smoothened; GLI transcription; PKA phosphorylation; Cilium segregation; ACUTE REGULATORY PROTEIN; IMPAIRED STRESS-RESPONSE; HORMONE-SENSITIVE LIPASE; SIDE-CHAIN CLEAVAGE; GENE-EXPRESSION; MITOCHONDRIAL PROTEIN; LUTEINIZING-HORMONE; MESSENGER-RNA; PROGENITOR CELLS; CHOLESTEROL TRAFFICKING;
D O I
10.1016/j.mce.2021.111265
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
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.
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页数:21
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