The paralemmin protein family: Identification of paralemmin-2, an isoform differentially spliced to AKAP2/AKAP-KL, and of palmdelphin, a more distantcytosolic relative

Paralemmin is a protein implicated in plasma membrane dynamics. Here we des cribe the identification of two new paralemmin-related proteins. A partial paralemmin homolog, palmdelphin, is predominantly cytosolic, unlike paralem min which is lipid-anchored to the plasma membrane through a C-terminal Caa X motif. We have mapped the mouse palmdelphin gene to distal chromosome 3 b etween Amy2 and Abcd3, in a region homologous to human chromosome 1p22-p21 where the human palmdelphin gene is located. We have also identified a seco nd paralemmin isoform, paralemmin-2. It is expressed from a gene on human c hromosome 9q31-q33 which ends only 33 kb upstream of the gene encoding the protein kinase A-binding protein, AKAP2/AKAP-KL. The closely adjacent paral emmin-2 and AKAP2 genes are functionally linked in a very unusual manner. C himeric mRNAs are expressed, apparently by RNA readthrough and differential splicing, that encode natural fusion proteins in which either the N-termin al coiled-coil region or nearly the complete sequence of paralemmin-2 excep t its C-terminal CaaX motif is fused to AKAP2/AKAP-KL. The N-terminal coile d-coil region is conserved in paralemmin-1, paralemmin-2/AKAP2, palmdelphin and a fourth, uncharacterized gene, suggesting that it is a modular functi onal domain. (C) 2001 Academic Press.