Presynaptic BK channel localization is dependent on the hierarchical organization of alpha-catulin and dystrobrevin and fine-tuned by XXXX @entity460 channels.

@entity70798 @entity2199 @entity40926 @entity40925 @entity72098 @entity72097 @entity460
BACKGROUND: Large conductance, @entity460 -activated BK channels regulate many important physiological processes, including smooth muscle excitation, hormone release and synaptic transmission. The biological roles of these channels hinge on their unique ability to respond synergistically to both voltage and cytosolic @entity460 elevations. Because @entity460 influx is meticulously regulated both spatially and temporally, the localization of BK channels near @entity460 channels is critical for their proper function. However, the mechanism underlying BK channel localization near @entity460 channels is not fully understood. RESULTS: We show here that in @entity2199 the localization of @entity70798 /BK channels to presynaptic terminals, where @entity40926 / @entity40925 @entity460 channels regulate neurotransmitter release, is controlled by the hierarchical organization of @entity72097 /a-catulin and @entity72098 /dystrobrevin, two proteins that interact with cortical cytoskeletal proteins. @entity72097 organizes a macromolecular @entity70798 channel complex at presynaptic terminals by direct physical interaction. @entity72098 contributes to the maintenance or stabilization of the complex at presynaptic terminals by interacting with @entity72097 . We also show that @entity70798 channels are functionally coupled with @entity40926 @entity460 channels, and that normal localization of @entity70798 to presynaptic terminals requires @entity40926 . In the absence of @entity40926 , @entity70798 clusters lose the localization specificity, thus accumulating inside and outside of presynaptic terminals. Moreover, @entity72097 is also similarly localized in @entity40926 mutants, consistent with the direct interaction between @entity72097 and @entity70798 . However, localization of @entity40926 at the presynaptic terminals is not dependent on either @entity72097 or @entity70798 . Taken together, our data strongly suggest that the absence of @entity40926 indirectly influences @entity70798 localization via the reorganization of cytoskeletal proteins. CONCLUSION: @entity72097 and @entity72098 , which interact with cortical cytoskeletal proteins, are required for the presynaptic punctate localization of @entity70798 in a hierarchical manner. In addition, @entity40926 @entity460 channels indirectly control the fidelity of @entity70798 puncta localization at presynaptic terminals. We suggest that the absence of @entity40926 leads to the reorganization of the cytoskeletal structure that includes @entity72097 , which in turn influences @entity70798 puncta localization.
