Multiple sorting systems for secretory granules ensure the regulated secretion of peptide hormones.
著者
Sun, Meng
渡部, 剛
(Watanabe, Tsuyoshi)
暮地本, 宙己
(Bochimoto, Hiroki)
Sakai, Yuko
鳥居, 征司
(Torii, Seiji)
竹内, 利行
(Takeuchi, Toshiyuki)
穂坂, 正博
(Hosaka, Masahiro)
上位タイトル
Traffic
Vol.14,
No.2
(2013.
2)
,p.205-
218
識別番号
ISSN
1398-9219
DOI
10.1111/tra.12029
その他
PMID:23171199
抄録
Prior to secretion, regulated peptide hormones are selectively sorted to secretory granules (SGs) at the trans-Golgi network (TGN) in endocrine cells. Secretogranin III (SgIII) appears to facilitate SG sorting process by tethering of protein aggregates containing chromogranin A (CgA) and peptide hormones to the cholesterol-rich SG membrane (SGM). Here, we evaluated the role of SgIII in SG sorting in AtT-20 cells transfected with small interfering RNA targeting SgIII. In the SgIII-knockdown cells, the intracellular retention of CgA was greatly impaired, and only a trace amount of CgA was localized within the vacuoles formed in the TGN, confirming the significance of SgIII in both the tethering of CgA-containing aggregates and the establishment of the proper SG morphology. Although the intracellular retention of proopiomelanocortin (POMC) was considerably impaired in SgIII-knockdown cells, residual adrenocorticotropic hormone (ACTH)/POMC was still localized to some few remaining SGs together with another granin protein, secretogranin II (SgII), and was secreted in a regulated manner. Biochemical analyses indicated that SgII bound directly to the SGM in a cholesterol-dependent manner and was able to retain the aggregated form of POMC, revealing a latent redundancy in the SG sorting and retention mechanisms, that ensures the regulated secretion of bioactive peptides.
