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The exocyst complex is an essential component of the mammalian constitutive secretory pathway.

Published version
Peer-reviewed

Type

Article

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Abstract

Secreted proteins fulfill a vast array of functions, including immunity, signaling, and extracellular matrix remodeling. In the trans-Golgi network, proteins destined for constitutive secretion are sorted into post-Golgi carriers which fuse with the plasma membrane. The molecular machinery involved is poorly understood. Here, we have used kinetic trafficking assays and transient CRISPR-KO to study biosynthetic sorting from the Golgi to the plasma membrane. Depletion of all canonical exocyst subunits causes cargo accumulation in post-Golgi carriers. Exocyst subunits are recruited to and co-localize with carriers. Exocyst abrogation followed by kinetic trafficking assays of soluble cargoes results in intracellular cargo accumulation. Unbiased secretomics reveals impairment of soluble protein secretion after exocyst subunit knockout. Importantly, in specialized cell types, the loss of exocyst prevents constitutive secretion of antibodies in lymphocytes and of leptin in adipocytes. These data identify exocyst as the functional tether of secretory post-Golgi carriers at the plasma membrane and an essential component of the mammalian constitutive secretory pathway.

Description

Keywords

Animals, Secretory Pathway, Exocytosis, Protein Transport, Golgi Apparatus, trans-Golgi Network, Proteins, Cell Membrane, Mammals

Journal Title

J Cell Biol

Conference Name

Journal ISSN

0021-9525
1540-8140

Volume Title

Publisher

Rockefeller University Press
Sponsorship
Isaac Newton Trust (Minute No: 21.23(i))
Wellcome Trust (210481/Z/18/Z)
BBSRC (BB/W005905/1)
Medical Research Council (MR/S007091/1)
MRC (MC_UU_00014/5)