DIFFERENTIAL EXPRESSION AND REGULATION OF MULTIPLE DYNAMINS

Dynamin is a GTP-, microtubule, and phospholipid-binding protein that is expressed primarily in brain. In Drosophila, the shibire gene encod es a homologue of dynamin; mutations in this gene result in a defect i n endocytosis, suggesting a function for dynamin in endocytic membrane traffic. In the present study we show that there are at least two dis tinct dynamin genes in mammals whose products are referred to as dynam ins I and II. The two dynamins are similar to each other (79% identity ) and are both equally homologous to the Drosophila shibire gene produ ct (66% identity). The highest degree of identity between dynamins is observed in their N-terminal halves, whereas their C termini exhibit l ittle homology. Transcripts of both dynamin genes are subject to at le ast two alternative splicing events, the first of which is identically found in both dynamins, whereas the second site of alternative splici ng is different between the two types of dynamins. The first alternati vely spliced sequence of the dynamins consists of an interior region t hat is present in two distinct but homologous forms in both dynamins, suggesting alternative use of exons in both genes at identical positio ns. The second site of alternative splicing results in the generation of different C termini in dynamin I and in the inclusion or exclusion of an interior four amino acid sequence in dynamin II. The two dynamin s exhibit remarkable differences in their tissue distribution and regu lation. Dynamin I is almost exclusively expressed in the central nervo us system Conversely, dynamin II is expressed ubiquitously in all tiss ues tested. Previous studies revealed that the GTPase activity of dyna min I is regulated by phosphorylation by protein kinase C in nerve ter minals. Expression of dynamins I and II by transfection in COS cells d emonstrates that only dynamin I but not dynamin II is a substrate for protein kinase C. Our data suggest a specialization in the endocytic f unctions and the regulation of dynamins between neural and non-neural tissues in mammals.