8.a.149.  The Cytoskeleton-associated Protein 4 (CKAP4) Family

Cytoskeleton-associated protein 4 (CKAP4) is a palmitoylated type II transmembrane protein localized to the endoplasmic reticulum (ER). Knockout (KO) of CKAP4 in HeLaS3 cells induced the alterations of mitochondrial structures and increased the number of ER-mitochondria contact sites. To understand the involvement of CKAP4 in mitochondrial functions, the binding proteins of CKAP4 were explored, enabling identification of the mitochondrial porin voltage-dependent anion-selective channel protein2 (VDAC2), which is localized to the outer mitochondrial membrane (Harada et al. 2020). Palmitoylation at Cys(100) of CKAP4 was required for the binding of CKAP4 to VDAC2. In CKAP4 KO cells, the binding of the inositol trisphosphate receptor (IP3R) to VDAC2 was enhanced, the intramitochondrial Ca2+ concentration increased, and the mitochondrial membrane potential decreased. In addition, the CKAP4 KO mutation decreased the oxidative consumption rate, in vitro cancer cell proliferation under low-glucose conditions, and in vivo xenograft tumor formation. The phenotypes were not rescued by a palmitoylation-deficient CKAP4 mutant. Thus, CKAP4 plays a role in maintaining mitochondrial functions by binding to VDAC2 at ER-mitochondria contact sites in a process that requires palmitoylation (Harada et al. 2020).


 

References:

Harada, T., R. Sada, Y. Osugi, S. Matsumoto, T. Matsuda, M. Hayashi-Nishino, T. Nagai, A. Harada, and A. Kikuchi. (2020). Palmitoylated CKAP4 regulates mitochondrial functions through an interaction with VDAC2 at ER-mitochondria contact sites. J Cell Sci 133:.

Vedrenne, C., D.R. Klopfenstein, and H.P. Hauri. (2005). Phosphorylation controls CLIMP-63-mediated anchoring of the endoplasmic reticulum to microtubules. Mol. Biol. Cell 16: 1928-1937.

Examples:

TC#NameOrganismal TypeExample
8.A.149.1.1

Cytoskeleton-associated protein 4, CKAP4, of 602 aas and one or two adjacent TMSs near the N-terminus. It mediates the anchoring of the endoplasmic reticulum to microtubules (Vedrenne et al. 2005). Palmitoylated CKAP4 regulates mitochondrial functions through an interaction with VDAC2 at ER-mitochondrion contact sites (Harada et al. 2020).

 

CKAP4 of Homo sapiens

 
8.A.149.1.2

Cytoskeleton-associated protein 4, CKAP4, of 426 aas and 1 TMS near the N-terminus.

CKAP4 of Carassius gibelio

 
8.A.149.1.3

Cytoskeleton-associated protein 4 isoform X2, CKAP4-X2, of 475 aas and 1 TMS near the N-terminus.

CKAP of Pimephales promelas (fathead minnow)