Ca2+ regulation of constitutive vesicle trafficking

Abstract

Constitutive vesicle trafficking is the default pathway used by all cells for movement of intracellular cargoes between subcellular compartments and in and out of the cell. Classically, constitutive trafficking was thought to be continuous and unregulated, in contrast to regulated secretion, wherein vesicles are stored intracellularly until undergoing synchronous membrane fusion following a Ca 2+ signal. However, as shown in the literature reviewed here, many continuous trafficking steps can be up- or down-regulated by Ca 2+ , including several steps associated with human pathologies. Notably, we describe a series of Ca 2+ pumps, channels, Ca 2+ -binding effector proteins, and their trafficking machinery targets that together regulate the flux of cargo in response to genetic alterations as well as baseline and agonist-dependent Ca 2+ signals. Here, we review the most recent advances, organized by organellar location, that establish the importance of these components in trafficking steps. Ultimately, we conclude that Ca 2+ regulates an expanding series of distinct mechanistic steps. Furthermore, the involvement of Ca 2+ in trafficking is complex. For example, in some cases, the same Ca 2+ effectors regulate surprisingly distinct trafficking steps, or even the same trafficking step with opposing influences, through binding to different target proteins.

Signaling Cascade Mediating the Effect of FTY720P on the Na+/K+ ATPase in LLC-PK1

“…Upon synthesis, the Na + /K + ATPase should translocate to the basal membrane to perform its functions properly. Rho kinase was shown to play a major role in the trafficking process [66], which is regulated by calcium and involves reorganization of the cytoskeleton [67,68].…”

The role of CaMKK2 in Golgi-associated vesicle trafficking

“…Here, we will discuss their regulation by CaM. The main calcium stores in the mammalian cell are the ER, Golgi and the lysosome [ 31 ]. Calcium plays a well-established role in vesicle trafficking and CaM is emerging as an additional regulatory complex [ 32 , 33 ].…”

“…The effectors of CaM that regulate endocytosis include calcineurin, a protein phosphatase, CaMKK2 and protein kinase C (PKC) [ 34–36 ]. Vesicle trafficking between the ER and Golgi is regulated by calcium through mechanisms that include Ca 2+ channels in the ER [ 31 ]. Vesicle formation is tightly regulated by the recruitment of membrane-binding and structural proteins that together form a coat of a defined size that envelope the membrane and create a bud that can be pinched off from the organelle.…”

“…Disruption of Ca 2+ signalling abrogates coat recruitment and vesicle formation for both anterograde and retrograde vesicle trafficking between these two organelles [ 37–40 ]. In this context, it is important to mention that the Golgi is a Ca 2+ storage organelle with a concentration gradient that ranges from 300 µM in the cis-Golgi to 100 µM in the trans-Golgi [ 31 ]. A transient localised increase in Ca 2+ concentration can be sensed by CaM ( K d = 0.5–5 µM), which results in a conformational change and interaction with target proteins [ 41 ].…”

Possible Association of Nucleobindin-1 Protein with Depressive Disorder in Patients with HIV Infection

“…Importantly, it is believed to be a novel pan-neuronal calcium handling marker [ 7 ], associated with cancers [ 8 ], and stimulating insulin secretion [ 9 ]. According to the literature, NUCB1 protein is implicated in Alzheimer’s disease [ 10 , 11 ], other neurodegenerative diseases, or cellular processes known to be dysregulated early in tauopathy pathogenesis [ 12 ] such as synaptic plasticity, proteostasis, glucose metabolism, and mitochondrial function. Recently, a paper indicated that an adult-viable mutant that completely disrupts the G protein α-subunit binding and activates NUCB1 plays a neuroprotective role in the Drosophila model [ 13 ] of neurodegenerative disease.…”