Redundant functions of RIM1α and RIM2α in Ca2+-triggered neurotransmitter release
Copyright policy )Redundant functions of RIM1α and RIM2α in Ca2+-triggered neurotransmitter release
Alpha-RIMs (RIM1alpha and RIM2alpha) are multidomain active zone proteins of presynaptic terminals. Alpha-RIMs bind to Rab3 on synaptic vesicles and to Munc13 on the active zone via their N-terminal region, and interact with other synaptic proteins via their central and C-terminal regions. Although RIM1alpha has been well characterized, nothing is known about the function of RIM2alpha. We now show that RIM1alpha and RIM2alpha are expressed in overlapping but distinct patterns throughout the brain. To examine and compare their functions, we generated knockout mice lacking RIM2alpha, and crossed them with previously produced RIM1alpha knockout mice. We found that deletion of either RIM1alpha or RIM2alpha is not lethal, but ablation of both alpha-RIMs causes postnatal death. This lethality is not due to a loss of synapse structure or a developmental change, but to a defect in neurotransmitter release. Synapses without alpha-RIMs still contain active zones and release neurotransmitters, but are unable to mediate normal Ca(2+)-triggered release. Our data thus demonstrate that alpha-RIMs are not essential for synapse formation or synaptic exocytosis, but are required for normal Ca(2+)-triggering of exocytosis.
- Yeshiva University United States
- The University of Texas Southwestern Medical Center United States
- University of Geneva Switzerland
- Saarland University Germany
- Ludwig-Maximilians-Universität München Germany
Male, Mice, Knockout, Heterozygote, Neurotransmitter Agents, Gene Expression Profiling, Neuromuscular Junction, Action Potentials, Brain, Nerve Tissue Proteins, Embryo, Mammalian, Electrophysiology, Mice, Gene Expression Regulation, GTP-Binding Proteins, Insulin Secretion, Animals, Insulin, Protein Isoforms, Calcium, RNA, Messenger
Male, Mice, Knockout, Heterozygote, Neurotransmitter Agents, Gene Expression Profiling, Neuromuscular Junction, Action Potentials, Brain, Nerve Tissue Proteins, Embryo, Mammalian, Electrophysiology, Mice, Gene Expression Regulation, GTP-Binding Proteins, Insulin Secretion, Animals, Insulin, Protein Isoforms, Calcium, RNA, Messenger
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