Cyclase Associated Protein

CAP (Cyclase Associated Protein) is a highly conserved and widely distributed protein. It was first described in yeast where it was identified as an adenylyl cyclase associated protein by genetic and biochemical methods. In addition to its requirement for the activation of adenylyl cyclase it was also essential for normal actin organisation by binding to G-actin and regulating actin filament dynamics. CAP has been found in plants, yeast, Dictyostelium, Drosophila and mammals. Loss of CAP results in defects in cell morphology, migration, endocytosis and development.

Higher eukaryotes have two homologs of CAP, CAP1 and CAP2, which are closely related. CAP1 shows a broad tissue distribution, whereas CAP2 is significantly expressed only in brain, heart and skeletal muscle, and in skin. CAP2 is found in the nucleus in undifferentiated myoblasts and at the M-line of differentiated myotubes. In Pam212, a mouse keratinocyte cell line, CAP2 is enriched in the nucleus. By contrast, CAP1 localises to stress fibers and F-actin rich regions such as lamellipodia in Pam212 cells. In human skin CAP2 is present in all living layers of the epidermis where it localises to the nuclei and to cell-cell junctions. Like other CAPs, CAP2 can sequester actin through its C-terminal domain.

The goal of my group is to understand the in vivo role of CAP2 using biochemical, genetic, molecular and cell biological methods.