Two Mammalian Sec16 Homologues Have Nonredundant Functions in Endoplasmic Reticulum (ER) Export and Transitional ER Organization

Abstract

Budding yeast Sec16 is a large peripheral endoplasmic reticulum (ER) membrane protein that functions in generating COPII transport vesicles and in clustering COPII components at transitional ER (tER) sites. Sec16 interacts with multiple COPII components. Although the COPII assembly pathway is evolutionarily conserved, Sec16 homologues have not been described in higher eukaryotes. Here, we show that mammalian cells contain two distinct Sec16 homologues: a large protein that we term Sec16L and a smaller protein that we term Sec16S. These proteins localize to tER sites, and an N-terminal region of each protein is necessary and sufficient for tER localization. The Sec16L and Sec16S genes are both expressed in every tissue examined, and both proteins are required in HeLa cells for ER export and for normal tER organization. Sec16L resembles yeast Sec16 in having a C-terminal conserved domain that interacts with the COPII coat protein Sec23, but Sec16S lacks such a C-terminal conserved domain. Immunoprecipitation data indicate that Sec16L and Sec16S are each present at multiple copies in a heteromeric complex. We infer that mammalian cells have preserved and extended the function of Sec16.

Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population

“…The SEC16B encodes long (Sec16L) and short (Sec16S) proteins, which are expressed ubiquitously in various tissues. 25 Sec16L and Sec16S are required for secretory cargo traffic from the endoplasmic reticulum to the Golgi apparatus. 25,26 We have reported that SCG3 and secretogranin II (SCG2) form secretory granules with orexin, neuropeptide Y (NPY) and proopiomelanocortin (POMC).…”

“…25 Sec16L and Sec16S are required for secretory cargo traffic from the endoplasmic reticulum to the Golgi apparatus. 25,26 We have reported that SCG3 and secretogranin II (SCG2) form secretory granules with orexin, neuropeptide Y (NPY) and proopiomelanocortin (POMC). 6,27 Thus, Sec16 may have a role in the transport of SCG3 and SCG2 together with orexin, NPY and POMC from the endoplasmic reticulum to the Golgi apparatus, and also in regulating the secretion of these appetiterelated peptides.…”

HSP105 interacts with GRP78 and GSK3 and promotes ER stress-induced caspase-3 activation

“…Of the new HSP105-interacting proteins that were identified, two, Sec16L and GRP78, are associated with the ER. Sec16L (KIAA0310) functions in the export of proteins from the ER [36]. GRP78 is particularly interesting because it is a key regulator of the cellular response to ER stress, as discussed in the introduction.…”

Régulation du transport vésiculaire par la courbure membranaire

“…Elle est soluble et inactive dans le cytoplasme lorsqu'elle est liée à une molécule de GDP (guanosine diphosphate). Lorsque le facteur d'échange Sec12 catalyse la substitution du GDP par un GTP (guanosine triphosphate), il provoque le changement de conformation de Sar1, qui ainsi activée s'attache à la membrane du RE [6] et se positionne dans un site d'export via son interaction avec la protéine Sec16 [7]. Sar1 recrute alors le premier étage du manteau COPII, l'hétérodimère Sec23/Sec24 qui à son tour recrute diverses protéines « passagères » diffusant dans la membrane pour peu qu'elles arborent un motif de reconnaissance spécifique.…”