Rab3D Is Critical for Secretory Granule Maturation in PC12 Cells

被引:12
作者
Kogel, Tanja [1 ]
Rudolf, Rudiger [2 ]
Hodneland, Erlend [1 ]
Copier, John [3 ]
Regazzi, Romano [4 ]
Tooze, Sharon A. [3 ]
Gerdes, Hans-Hermann [1 ,2 ]
机构
[1] Univ Bergen, Dept Biomed, Bergen, Norway
[2] Heidelberg Univ, Interdisciplinary Ctr Neurobiol, Heidelberg, Germany
[3] London Res Inst Canc Res United Kingdom, Lincolns Inn Fields Labs, London, England
[4] Univ Lausanne, Dept Fundamental Neurosci, CH-1000 Lausanne, Switzerland
关键词
AP-1 ADAPTER COMPLEX; MYOSIN VA; NEUROENDOCRINE CELLS; SECRETOGRANIN-II; LINKS RAB27A; PROTEIN; EXOCYTOSIS; ACTIN; BIOGENESIS; TRANSPORT;
D O I
10.1371/journal.pone.0057321
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Neuropeptide-and hormone-containing secretory granules (SGs) are synthesized at the trans-Golgi network (TGN) as immature secretory granules (ISGs) and complete their maturation in the F-actin-rich cell cortex. This maturation process is characterized by acidification-dependent processing of cargo proteins, condensation of the SG matrix and removal of membrane and proteins not destined to mature secretory granules (MSGs). Here we addressed a potential role of Rab3 isoforms in these maturation steps by expressing their nucleotide-binding deficient mutants in PC12 cells. Our data show that the presence of Rab3D(N135I) decreases the restriction of maturing SGs to the F-actin-rich cell cortex, blocks the removal of the endoprotease furin from SGs and impedes the processing of the luminal SG protein secretogranin II. This strongly suggests that Rab3D is implicated in the subcellular localization and maturation of ISGs.
引用
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页数:11
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