Membrane targeting of L-type calcium channels. Role of palmitoylation in the subcellular localization of the beta2a subunit - PubMed (original) (raw)

Comparative Study

. 1998 Sep 4;273(36):23590-7.

doi: 10.1074/jbc.273.36.23590.

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Comparative Study

Membrane targeting of L-type calcium channels. Role of palmitoylation in the subcellular localization of the beta2a subunit

A J Chien et al. J Biol Chem. 1998.

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Abstract

In this study, we report that palmitoylation was a critical determinant of the subcellular localization of the rat beta2a subunit of voltage-dependent calcium channels. Immunohistochemical staining of transfected cells revealed that a palmitoylation-deficient beta2a subunit exhibited a diffuse intracellular staining pattern, in contrast to the plasma membrane distribution seen with the wild-type beta2a subunit. Unexpectedly, mutations in regions distal to the palmitoylation sites at Cys3 and Cys4 affected palmitoylation of the beta2a protein. Mutations in an src homology 3 motif of the beta2a subunit affected both palmitoylation and subcellular localization of the beta2a protein. A mutation in the beta interaction domain, which disrupted interactions between the expressed alpha1 and beta subunits, also resulted in a decreased palmitoylation and diffuse intracellular localization of the beta2a protein. Studies of chimeric proteins revealed that the 16-amino acid N terminus of the beta2a subunit was sufficient to confer palmitoylation to the nonpalmitoylated beta1b and beta3 isoforms. However, palmitoylation of chimeric beta subunits was by itself insufficient to restore the plasma membrane localization observed with the wild-type beta2a protein. Treatment of transfected cells with brefeldin A increased the amount of palmitic acid incorporated in the beta2a protein, suggesting that palmitoylation of beta2a occurs during or shortly after protein synthesis. Two other beta2 variants, the rabbit beta2a and beta2b, which lack the palmitoylation sties at Cys3 and Cys4, exhibited a diffuse intracellular staining pattern and were not palmitoylated.

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