High impact information on Kcnip1

• Here we report a 2.0 Angstrom crystal structure of the core domain of KChIP1 (KChIP1*) in complex with the N-terminal fragment of Kv4.2 (Kv4.2N30) [1].
• Four EF-hands from each KChIP1 form each shell of the clam [1].
• The binding of KChIP facilitates a redistribution of Kv4 protein to the cell surface, producing a large increase in current along with significant changes in channel gating kinetics [2].
• KChIP proteins regulate Shal, Kv4.x, channel expression by binding to a conserved sequence at the N terminus of the subunit [2].
• These studies point to an essential role for KChIPs in determining both the biophysical and molecular characteristics of Kv4 channels and provide a molecular basis for the dramatic phenotype of KChIP knockout mice [3].

Biological context of Kcnip1

• KChIP co-expression also causes fundamental changes in Kv4.2 steady-state expression levels, phosphorylation, detergent solubility, and stability that reconstitute the molecular properties of Kv4.2 in native cells [3].
• Considering the importance of alternative splicing to the quantitative features of KChIP gating modulation, a previously uncharacterized splice form of KChIP1 was functionally characterized [4].
• Day-night changes in downstream regulatory element antagonist modulator/potassium channel interacting protein activity contribute to circadian gene expression in pineal gland [5].

Anatomical context of Kcnip1

• 3. For example, immunoreactivity for KChIP1 and Kv4.3 is concentrated in the somata and dendrites of hippocampal, striatal, and neocortical interneurons [6].
• Electron microscopic analysis revealed that KChIP1 and Kv4.2 immunoreactivity is concentrated along the plasma membrane of cerebellar granule cell somata and dendrites [7].
• In synaptic glomeruli, KChIP1 and Kv4.2 immunoreactivity is concentrated along the granule cell dendritic membrane, but is not concentrated at postsynaptic densities [7].
• Taken together, these data suggest that A-type potassium channels containing Kv4.2 and KChIP1, and perhaps also KChIP3 and 4, play a critical role in regulating postsynaptic excitability at the cerebellar mossy-fiber/granule cell synapse [7].
• Thus, palmitoylation of the KChIP auxiliary subunits controls plasma membrane localization of their associated channels [8].

Associations of Kcnip1 with chemical compounds

• The features of KChIP1b modulation of Kv4 channels are likely to be conserved in mammals and demonstrate a role for the KChIP1 NH2-terminal region in the regulation of closed inactivation gating [4].
• Compared with another transient potassium current formed by Kv1.1/Kvbeta1, Kv4.3/KChIP1 current was much more sensitive to arachidonic acid [9].

Other interactions of Kcnip1

• Kv4.2 and KChIP1 were highly expressed in GCs in rostral cerebellum, whereas Kv4.3 was more highly expressed in GCs in caudal cerebellum [7].
• Light and electron microscopic analysis of KChIP and Kv4 localization in rat cerebellar granule cells [7].

Analytical, diagnostic and therapeutic context of Kcnip1

• Association between KChIP1 and Kv4.2 or Kv4.3 was not altered in the presence of 10 microm ETYA as measured by immunoprecipitation and association-dependent growth in yeast [9].

References