Increased transmitter release and aberrant synapse morphology in a Drosophila calmodulin mutant.
The ubiquitous calcium-binding protein calmodulin (CaM) has been implicated in the development and function of the nervous system in a variety of eukaryotic organisms. We have generated mutations in the single Drosophila Calmodulin (Cam) gene and examined the effects of these mutations on behavior, synaptic transmission at the larval neuromuscular junction, and structure of the larval motor nerve terminal. Flies hemizygous for Cam3c1, a mutation in the first Ca2+-binding site, exhibit behavioral, neurophysiological, and neuroanatomical abnormalities. In particular, adults exhibit defects in locomotion, coordination, and flight. Larvae exhibit increased neurotransmitter release from the motor nerve terminal at low [Ca2+] in the presence of the K+ channel-blocking drug quinidine. In addition, synaptic bouton structure at motor nerve terminals is altered. These effects are distinct from those produced by altering the activity of the CaM target enzymes CaM-activated kinase II (CaMKII) and CaM-activated adenylyl cyclase (CaMAC). Furthermore, previous in vitro studies of mutant Cam3c1 demonstrated that although its Ca2+ affinity is decreased, Cam3c1 protein can activate CaMKII, CaMAC, and CaM-activated phosphatase calcineurin in a manner similar to wild-type CaM. Thus, the Cam3c1 mutation might affect Ca2+ buffering or interfere with the activation or inhibition of a CaM target distinct from CaMKII or CaMAC.
Arredondo
L
L
Department of Biochemistry and Cell Biology, Rice University, Houston, Texas 77005-1892, USA.
Nelson
H B
HB
Beckingham
K
K
Stern
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001522:Behavior, Animal; D002147:Calmodulin / Q000737:chemistry / Q000235:genetics*; D004330:Drosophila / Q000196:embryology / Q000235:genetics*; D007814:Larva / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission
D002147:Calmodulin