Neuroscience
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Calcium (Ca2+) is an essential component in intracellular signaling of brain cells, and its control mechanisms are of great interest in biological systems. Ca2+ can signal differently in neurons and glial cells using the same intracellular pathways or cell membrane structural components. These types of machinery are responsible for entry, permanence, and removal of Ca2+ from the cellular environment and are of vital importance for brain homeostasis. This review highlights the importance of Ca2+ in neuronal and glial cell physiology as well as aspects of learning, memory, and Alzheimer's disease, focusing on the involvement of L-type voltage-gated Ca2+ channels.
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Review
The Control of Neuronal Calcium Homeostasis by SNAP-25 and its Impact on Neurotransmitter Release.
The process of neurotransmitter release is central to the control of cell-to-cell communication in brain. SNAP-25 is a component of the SNARE complex, which, together with syntaxin-1 and synaptobrevin, mediates synaptic vesicle fusion with the plasma membrane. ⋯ Consistently, reduced levels of the protein affect presynaptic calcium homeostasis and result in pathologically enhanced glutamate exocytosis. The SNAP-25-dependent alterations of synaptic calcium dynamics may have direct impact on the development of neuropsychiatric disorders where the Snap-25 gene has been found to be involved.
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Synaptosomal Associated Protein-25 kilodaltons (SNAP-25) is an integral member of the SNARE complex. This complex is essential for calcium-triggered synaptic vesicular fusion and release of neurotransmitters into the synaptic cleft. In addition to neurotransmission, SNAP-25 is associated with insulin release, the regulation of intracellular calcium, and neuroplasticity. ⋯ We believe investigation of SNAP-25 is important for understanding both normal behavior and some aspects of the pathophysiology of behavior seen with psychiatric disorders. The wealth of information from both animal and human studies on SNAP-25 offers an excellent opportunity to use a bi-directional research approach. Hypotheses generated from genetically manipulated mice can be directly tested in human postmortem tissue, and, conversely, human genetic and postmortem findings can improve and validate animal models for psychiatric disorders.
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SNARE-complexes drive the fusion of membrane-bound vesicles with target membranes or with each other (homotypic fusion). The SNARE-proteins are subdivided into Qa, Qb, Qc and R-SNAREs depending on their position in the four-helical SNARE-bundle. Here, we review the SNAP-25 protein sub-family, which includes both the Qb and Qc SNARE-domains within a single protein. ⋯ SNAP-29 is present on intracellular membranes and performs functions in autophagosome-to-lysosome fusion, among others. An overlapping function for SNAP-47 was described; in addition, SNAP-47 mediates postsynaptic AMPA-receptor insertion. Overall, the presence of two SNARE-domains confers members of this family the ability to associate to different Qa and R-SNAREs and drive diverse membrane fusion reactions; one member of the family, SNAP-25, has been devoted entirely to Ca2+-triggered fusion and has taken on a number of additional, regulatory roles.
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Review
Mechanisms of Neurological Dysfunction in GOSR2 Progressive Myoclonus Epilepsy, a Golgi SNAREopathy.
Successive fusion events between transport vesicles and their target membranes mediate trafficking of secreted, membrane- and organelle-localised proteins. During the initial steps of this process, termed the secretory pathway, COPII vesicles bud from the endoplasmic reticulum (ER) and fuse with the cis-Golgi membrane, thus depositing their cargo. This fusion step is driven by a quartet of SNARE proteins that includes the cis-Golgi t-SNARE Membrin, encoded by the GOSR2 gene. ⋯ However, given the ubiquitous and essential function of ER-to-Golgi transport, why GOSR2 mutations cause neurological dysfunction and not lethality or a broader range of developmental defects has remained an enigma. Here we highlight new work that has shed light on this issue and incorporate insights into canonical and non-canonical secretory trafficking pathways in neurons to speculate as to the cellular and molecular mechanisms underlying GOSR2 PME. This article is part of a Special Issue entitled: SNARE proteins: a long journey of science in brain physiology and pathology: from molecular.