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Neuronal junctophilins recruit specific Ca_V and RyR isoforms to ER-PM junctions and functionally alter Ca_V2.1 and Ca_V2.2.

ABSTRACT: Junctions between the endoplasmic reticulum and plasma membrane that are induced by the neuronal junctophilins are of demonstrated importance, but their molecular architecture is still poorly understood and challenging to address in neurons. This is due to the small size of the junctions and the multiple isoforms of candidate junctional proteins in different brain areas. Using colocalization of tagged proteins expressed in tsA201 cells, and electrophysiology, we compared the interactions of JPH3 and JPH4 with different calcium channels. We found that JPH3 and JPH4 caused junctional accumulation of all the tested high-voltage-activated Ca_V isoforms, but not a low-voltage-activated Ca_V. Also, JPH3 and JPH4 noticeably modify Ca_V2.1 and Ca_V2.2 inactivation rate. RyR3 moderately colocalized at junctions with JPH4, whereas RyR1 and RyR2 did not. By contrast, RyR1 and RyR3 strongly colocalized with JPH3, and RyR2 moderately. Likely contributing to this difference, JPH3 binds to cytoplasmic domain constructs of RyR1 and RyR3, but not of RyR2.

SUBMITTER: Perni S

PROVIDER: S-EPMC8046434 | biostudies-literature |

REPOSITORIES: biostudies-literature

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