DreEX0027747 @ danRer10

The authors generated stably transfected Clone 9 cells expressing full-length cDNAs of six different spliced forms of the three dynamin genes (Dnm1, Dnm2, and Dnm3) tagged with green fluorescent protein. The investigated splice variants are: Dnm1 (with mutually exclusive exon 10a (MmuEX6100535) or exon 10b (MmuEX0015279), Dnm2 (with/without cassette exon (MmuEX0015304), and Dnm3 (with/without cassette exon MmuEX0015311). Confocal or fluorescence microscopy of these transfected cells revealed that many of the dynamin proteins associate with distinct membrane compartments, which include clathrin-coated pits at the plasma membrane and the Golgi apparatus, and several undefined vesicle populations.

[Negative results]. Dynamin-1 (Dnm1) encodes a large multimeric GTPase necessary for activity-dependent membrane recycling in neurons, including synaptic vesicle endocytosis. Mice heterozygous for a novel spontaneous Dnm1 mutation--fitful--experience recurrent seizures, and homozygotes have more debilitating, often lethal seizures in addition to severe ataxia and neurosensory deficits. Fitful is a missense mutation in an exon that defines the DNM1a isoform (uses Exon 10a (MmuEX6100535)), leaving intact the alternatively spliced exon that encodes DNM1b (uses exon 10b (MmuEX0015279). The expression of the corresponding alternate transcripts is developmentally regulated, with DNM1b expression highest during early neuronal development and DNM1a expression increasing postnatally with synaptic maturation. Mutant DNM1a does not efficiently self-assemble into higher order complexes known to be necessary for proper dynamin function, and it also interferes with endocytic recycling in cell culture. In mice, the mutation results in defective synaptic transmission characterized by a slower recovery from depression after trains of stimulation. The DNM1a and DNM1b isoform pair is highly conserved in vertebrate evolution, whereas invertebrates have only one isoform. The authors speculate that the emergence of more specialized forms of DNM1 may be important in organisms with complex neuronal function. The DNM1a and DNM1b isoforms show similar complex formation ability and localization.