Figure 8.

Biological processes and cellular components that might be affected by PAM haploinsufficiency in pituitary hormone-secreting cells. The trafficking of integral membrane PAM and pituitary hormones through the regulated secretory pathway is depicted. Immature secretory granules (iSGs) budding from the trans-Golgi network (TGN) contain prohormones and processing enzymes like the prohormone convertases (PCs), granins [chromogranins A and B (ChgA/B) and secretogranins II and II], and PAM. Mature secretory granules (mSGs) release their soluble content during regulated exocytosis (the yellow lightning bolt represents the external stimulus triggering secretion). Although PAM appears on the cell surface during exocytosis, its rapid endocytosis means that very little PAM remains on the plasma membrane at the steady state. Cleavage by secretase-like enzymes can generate a soluble, cytosolic fragment of PAM that can enter the nucleus, where it relays information about the status of the secretory granule pool. Several in vitro studies have shown that PAM misexpression can affect a variety of steps in the regulated secretory pathway; these are highlighted in red in the cartoon. ER, endoplasmic reticulum; GH, growth hormone; MVB, multivesicular body.