title: Exploring the dominant role of Cav1 channels in signalling to the nucleus.
abstract: Calcium is important in controlling nuclear gene expression through the activation of multiple signal-transduction pathways in neurons. Compared with other voltage-gated calcium channels, Ca(V)1 channels demonstrate a considerable advantage in signalling to the nucleus. In this review, we summarize the recent progress in elucidating the mechanisms involved. Ca(V)1 channels, already advantaged in their responsiveness to depolarization, trigger communication with the nucleus by attracting colocalized clusters of activated CaMKII (Ca(2+)/calmodulin-dependent protein kinase II). Ca(V)2 channels lack this ability, but must work at a distance of >1 μm from the Ca(V)1-CaMKII co-clusters, which hampers their relative efficiency for a given rise in bulk [Ca(2+)](i) (intracellular [Ca(2+)]). Moreover, Ca(2+) influx from Ca(V)2 channels is preferentially buffered by the ER (endoplasmic reticulum) and mitochondria, further attenuating their effectiveness in signalling to the nucleus.
authors.affiliation: NYU Neuroscience Institute, NYU Langone Medical Center, New York, NY 10016, USA. huan.ma@nyumc.org
authors.forename: Huan
authors.initials: H
authors.lastname: Ma
authors.forename: Samuel
authors.initials: S
authors.lastname: Cohen
authors.forename: Boxing
authors.initials: B
authors.lastname: Li
authors.forename: Richard W
authors.initials: RW
authors.lastname: Tsien
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D020013:Calcium Signaling; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002529:Cerebellar Nuclei / Q000187:drug effects / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004789:Enzyme Activation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017783:Superior Cervical Ganglion / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D017362:Cyclic AMP Response Element-Binding Protein; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium