Polyvalent cations and hypertonic shrinking of presynaptic endings lead to calcium-independent exocytosis in various synapses. In the present study we have investigated the contribution of integrins to this phenomenon. It was found that hypertonic shrinking, polyvalent cations ruthenium red and gadolinium results in dose-dependent calcium-independent neurotransmitter release in rat brain synaptosomes. The exocytotic mechanism of neurotransmitter release induced by 300 microM gadolinium was additionally verified by the fluorescent dye FM2-10. We found that 200 microM of RGDS peptide, an inhibitor of integrins, decreased polyvalent gadolinium-induced [3H]D: -aspartate release by 26%. This compound had no effect upon hypertonicity-induced release. The peptide RGES, a negative control for RGDS; genistein, an inhibitor of tyrosine kinases; and citrate, an inhibitor of lanthanides-induced aggregation were ineffective in both cases. Therefore, we have shown that integrins did not influence hypertonicity-evoked [3H]D: -aspartate release, but partially mediated that evoked by gadolinium ions.
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http://dx.doi.org/10.1007/s11064-007-9585-5 | DOI Listing |
Methods Mol Biol
January 2025
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA.
Many membrane proteins on the cell surface are constantly internalized from, and re-delivered to, the plasma membrane. This endocytic cycling, which relies on accurate SNARE-mediated fusion of vesicles containing cargo proteins, is highly important for the function of many proteins such as signaling receptors. While the SNARE proteins that mediate fusion during specific events, such as neurotransmitter and hormone release, in mammalian cells has been heavily studied, the SNARE proteins that mediate surface delivery of specific cargo such as the receptors for these released factors are still not known.
View Article and Find Full Text PDFMethods Mol Biol
January 2025
Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha, Qatar.
Vesicle fusion induces neurotransmitter release, orchestrated by synaptotagmin-1 (Syt-1) as a Ca sensor. However, the precise molecular mechanisms of Syt-1 remain controversial, with various and competing models proposed based on different ionic strengths. Syt-1, residing on the vesicle membrane alongside anionic phospholipids such as phosphatidylserine (PS), undergoes Ca-induced binding to its own vesicle membrane, known as the cis-interaction, which prevents the trans-interaction of Syt-1 with the plasma membrane.
View Article and Find Full Text PDFMethods Mol Biol
January 2025
Department of Biochemistry, Weill Cornell Medicine, New York, NY, USA.
Complexins are a family of small presynaptic proteins that regulate neurotransmitter release at nerve terminals and are highly conserved in evolution. While direct interactions with SNARE proteins are critical for all complexin functions, binding of their disordered C-terminal domains (CTD) to membranes, especially to synaptic vesicle membranes, is essential for the ability of complexin to inhibit vesicle release. Furthermore, while some complexin CTDs possess an endogenous affinity for membranes, other complexin isoforms are subject to lipidation at their C-termini, which is presumed to confer additional membrane binding.
View Article and Find Full Text PDFClin Neuropharmacol
January 2025
MedStar Georgetown University Hospital, Washington, DC.
Introduction: Adjunctive therapies to treat OFF episodes resulting from long-term levodopa treatment in Parkinson disease (PD) are hampered by safety and tolerability issues. Istradefylline offers an alternative mechanism (adenosine A2A receptor antagonist) and therefore potentially improved tolerability.
Methods: A systematic review of PD adjuncts published in 2011 was updated to include randomized controlled trials published from January 1, 2010-April 15, 2019.
bioRxiv
December 2024
Department of Biology, University of Miami, 1301 Memorial Drive, Coral Gables, FL 33146.
Animals alter their behavior in response to changes in the environment. Upon encountering hyperosmotic conditions, the nematode worm initiates avoidance and cessation of egg-laying behavior. While the sensory pathway for osmotic avoidance is well-understood, less is known about how egg laying is inhibited.
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