Sec16 in conventional and unconventional exocytosis: Working at the interface of membrane traffic and secretory autophagy?
Sec16 is classically perceived to be a scaffolding protein localized to the transitional endoplasmic reticulum (tER) or the ER exit sites (ERES), and has a conserved function in facilitating coat protein II (COPII) complex-mediated ER exit. Recent findings have, however, pointed toward a role for Sec16 in unconventional exocytosis of certain membrane proteins, such as the Cystic fibrosis transmembrane conductance regulator (CFTR) in mammalian cells, and possibly also α-integrin in certain contexts of Drosophila development. In this regard, Sec16 interacts with components of a recently deciphered pathway of stress-induced unconventional exocytosis, which is dependent on the tether protein Golgi reassembly stacking proteins (GRASPs) and the autophagy pathway. Intriguingly, Sec16 also appears to be post-translationally modified by autophagy-related signaling processes. Sec16 is known to be phosphorylated by the atypical extracellular signal regulated kinase 7 (Erk7) upon serum and amino acid starvation, both represent conditions that trigger autophagy. Recent work has also shown that Sec16 is phosphorylated, and thus regulated by the prominent autophagy-initiating Unc-51-like autophagy activating kinase 1 (Ulk1), as well as another autophagy modulator Leucine-rich repeat kinase 2 (Lrrk2). The picture emerging from Sec16's network of physical and functional interactors allows the speculation that Sec16 is situated (and may in yet undefined ways function) at the interface between COPII-mediated exocytosis of conventional vesicular traffic and the GRASP/autophagy-dependent mode of unconventional exocytosis.
Departmentof Biochemistry, Yong Loo Lin School of Medicine, National University Health System, Singapore.|NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.
Bor Luen
http://orcid.org/0000-0002-1925-636X
BL
Tang
D000818:Animals; D001343:Autophagy; D002462:Cell Membrane / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005089:Exocytosis; D006801:Humans; D021381:Protein Transport; D033921:Vesicular Transport Proteins / Q000378:metabolism*
D033921:Vesicular Transport Proteins