Abstract
Membrane trafficking is essential for processing and transport of proteins and lipids and to establish cell compartmentation and tissue organization. Cells respond to their needs and control the quantity and quality of protein secretion accordingly. In this review, we focus on a particular membrane trafficking route from the trans-Golgi network (TGN) to the cell surface: protein kinase D (PKD)-dependent pathway for constitutive secretion mediated by carriers of the TGN to the cell surface (CARTS). Recent findings highlight the importance of lipid signaling by organelle membrane contact sites (MCSs) in this pathway. Finally, we discuss our current understanding of multiple signaling pathways for membrane trafficking regulation mediated by PKD, G protein-coupled receptors (GPCRs), growth factors, metabolites, and mechanosensors.
Highlights
trans-Golgi network (TGN)-to-Plasma Membrane TransportCells synthesize complex biological molecules—nucleic acids, carbohydrates, proteins, and lipids—to support life
We have reviewed here our current understanding of how TGN-to-cell surface membrane trafficking and constitutive protein secretion is controlled, with a special emphasis on the mechanisms that regulate CARTS formation through protein kinase D (PKD)
The establishment of PKD as a master regulator of transport carrier formation at the TGN was followed by a number of breakthroughs that extended the role of PKD in regulating Golgi lipid homeostasis
Summary
Cells synthesize complex biological molecules—nucleic acids, carbohydrates, proteins, and lipids—to support life. Eukaryotic cells have evolved a complex intracellular organization, which is facilitated by the existence of membrane-bound organelles: functional entities with a well-defined biochemical composition Because of this compartmentalization of biochemical reactions, eukaryotic cells can efficiently and simultaneously perform a large number of biological functions. The correct delivery of cargo proteins to the cell surface or their release to the extracellular space is fundamental to cell-to-cell communication, which influences virtually all cellular functions Included in these cargo proteins are the cell surface receptors such as integrins (required for cell adhesion and migration), cytokines and growth factors (with roles in cell proliferation, differentiation, and wound healing), extracellular matrix (ECM) proteins such as collagens and matrix metalloproteinases (needed for the assembly of tissues in multicellular organisms), neurotransmitters (necessary for neural functions), or mucins (needed to create protective barriers in epithelial tissues) [2].
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