Voltage-gated Cav channels mediate activity-dependent Ca2+ signals required for gene transcription and neurotransmission. Ca2+-dependent inactivation and facilitation (CDI and CDF, respectively) allow Cav channels to adjust Ca2+ influx according to neuronal activity, thereby fine-tuning Ca2+ signals that control neuronal excitability and synaptic plasticity. The rationale for the proposed research is that defining how Cav channels generate and maintain Ca2+ signals will answer longstanding questions regarding the heterogeneous properties of Cav channels in neurons and enable new mechanistic inquiries into the roles of specific Cav channels in orchestrating the normal development and function of the nervous system. The expected outcomes of the proposed research are: establishment of a new role for calretinin as a dynamic regulator of effectors including Cav2.
1 (Aim 1); and elucidation of a mechanism responsible for the long-lasting properties and functional impact of neuronal Cav1 L-type currents (Aim 2). We believe that the proposed research will make a lasting and positive impact: the Cav channel regulatory mechanisms it will define will likely facilitate the development of novel therapeutics for neurological and neuropsychiatric disorders resulting from dysregulation of neuronal Ca2+ signals.
The proposed research will characterize the mechanisms and physiological significance of factors that modulate voltage-gated Ca2+ channels neurons. We will elucidate new cellular and molecular mechanisms, which may be altered in neurological and neuropsychiatric diseases.
|Krueger, Jamie N; Moore, Shannon J; Parent, Rachel et al. (2017) A novel mouse model of the aged brain: Over-expression of the L-type voltage-gated calcium channel CaV1.3. Behav Brain Res 322:241-249|
|Zhu, Lu; Almaça, Joana; Dadi, Prasanna K et al. (2017) ?-arrestin-2 is an essential regulator of pancreatic ?-cell function under physiological and pathophysiological conditions. Nat Commun 8:14295|
|Wang, Xiaohan; Marks, Christian R; Perfitt, Tyler L et al. (2017) A novel mechanism for Ca2+/calmodulin-dependent protein kinase II targeting to L-type Ca2+ channels that initiates long-range signaling to the nucleus. J Biol Chem 292:17324-17336|
|Wang, Shiyi; Stanika, Ruslan I; Wang, Xiaohan et al. (2017) Densin-180 Controls the Trafficking and Signaling of L-Type Voltage-Gated Cav1.2 Ca2+ Channels at Excitatory Synapses. J Neurosci 37:4679-4691|
|Wongrakpanich, Amaraporn; Morris, Angie S; Geary, Sean M et al. (2017) Surface-modified particles loaded with CaMKII inhibitor protect cardiac cells against mitochondrial injury. Int J Pharm 520:275-283|
|Yang, Tian; Scholl, Elizabeth S; Pan, Ning et al. (2016) Expression and Localization of CaBP Ca2+ Binding Proteins in the Mouse Cochlea. PLoS One 11:e0147495|
|Hardie, Jason; Lee, Amy (2016) Decalmodulation of Cav1 channels by CaBPs. Channels (Austin) 10:33-7|
|Haeseleer, Françoise; Williams, Brittany; Lee, Amy (2016) Characterization of C-terminal Splice Variants of Cav1.4 Ca2+ Channels in Human Retina. J Biol Chem 291:15663-73|
|Sinha, Raunak; Lee, Amy; Rieke, Fred et al. (2016) Lack of CaBP1/Caldendrin or CaBP2 Leads to Altered Ganglion Cell Responses. eNeuro 3:|
|Thomas, Jessica R; Lee, Amy (2016) Measuring Ca2+-Dependent Modulation of Voltage-Gated Ca2+ Channels in HEK-293T Cells. Cold Spring Harb Protoc 2016:pdb.prot087213|
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