PACS-1 and adaptor protein-1 mediate ACTH trafficking to the regulated secretory pathway

Journal Article · Sat Dec 15 04:00:00 EST 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.11.085· OSTI ID:23103650

Dirk, Brennan S.; End, Christopher; Pawlak, Emily N.; Van Nynatten, Logan R.; Jacob, Rajesh Abraham; Heit, Bryan

Highlights: • PACS-1 and AP-1 play critical roles in targeting ACTH to the regulated secretory pathway. • PACS-1 and AP-1 promote the intracellular storage of ACTH. • In the absence of PACS-1 and AP-1, ACTH is constitutively secreted. • PACS-1 localizes to ACTH-positive vesicles in an AP-1-dependent manner. The regulated secretory pathway is a specialized form of protein secretion found in endocrine and neuroendocrine cell types. Pro-opiomelanocortin (POMC) is a pro-hormone that utilizes this pathway to be trafficked to dense core secretory granules (DCSGs). Within this organelle, POMC is processed to multiple bioactive hormones that play key roles in cellular physiology. However, the complete set of cellular membrane trafficking proteins that mediate the correct sorting of POMC to DCSGs remain unknown. Here, we report the roles of the phosphofurin acidic cluster sorting protein – 1 (PACS-1) and the clathrin adaptor protein 1 (AP-1) in the targeting of POMC to DCSGs. Upon knockdown of PACS-1 and AP-1, POMC is readily secreted into the extracellular milieu and fails to be targeted to DCSGs.

• OSTI ID: 23103650
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1-4 Vol. 507; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACTH
CELL CONSTITUENTS
PHYSIOLOGY
SECRETION