ENHANCED NEUROTRANSMITTER RELEASE IS ASSOCIATED WITH REDUCTION OF NEURONAL BRANCHING IN A DROSOPHILA MUTANT OVEREXPRESSING FREQUENIN

Frequenin is a Drosophila Ca2+ binding protein whose overexpression ca uses a chronic facilitation of transmitter release at the larval neuro muscular junction and multiple firing of action potentials. These func tional abnormalities are similar to those found in other hyperexcitabl e mutants (Shaker, ether-a-gogo, Hyperkinetic) which, in turn, exhibit increased branching at the motor nerve endings. We report here that m utants which overexpress frequenin have motor nerve terminals with red uced number and length of branches as well as number of synaptic bouto ns. Similar defects are observed in transgenic flies which have additi onal copies of the frequenin gene indicating that the phenotype can be adscribed to the overexpression of the protein. The ultrastructure of boutons, however, appears indistinguishable from wild type. In additi on, we show here that frequenin overexpression leads also to a down re gulation of Shaker proteins expression. The contrast between the obser vations in frequenin and the other hyperexcitable mutants indicates th at nerve terminal morphology and enhanced transmitter release do not h ave a direct causal relationship.