The ALS-related σ1R E102Q Mutant Eludes Ligand Control and Exhibits Anomalous Response to Calcium.

ABSTRACT: Sigma receptor type 1 (σ1R) is a transmembrane protein expressed throughout the central nervous system and in certain peripheral tissues. The human σ1R E102Q mutation causes juvenile amyotrophic lateral sclerosis (ALS), likely by inducing a series of alterations in calcium efflux from the endoplasmic reticulum (ER) to mitochondria that affects calcium homeostasis and cellular survival. Here, we report the influence of calcium on σ1R E102Q associations with glutamate N-methyl-D-aspartate receptors (NMDARs), binding immunoglobulin protein (BiP), and transient receptor potential calcium channels A1, V1, and M8. The mutant protein inhibited the binding of calmodulin to these calcium channels and interacted less with BiP than wild-type σ1R, thereby contributing to calcium homeostasis dysfunctio

SUBMITTER: Rodriguez-Munoz M 

PROVIDER: S-EPMC7582951 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature