Drosophila lacking the Cdk5 activator, p35, display defective axon guidance, age-dependent behavioral deficits and reduced lifespan.
The cyclin-dependent kinase Cdk5 has attracted a great deal of attention both because of its roles in cell migration and axon patterning, and the extensive data implicating it in adult-onset neurodegeneration in mammals. Both the kinase activity and the biological effects of Cdk5 are absolutely dependent on association with an activating subunit, called p35. We show here that Drosophila lacking the Cdk5 activator, D-p35, display a wide range of defects in embryonic axon patterning. We further show that, while viable and fertile, p35 mutant adults display progressive, age-dependent loss of motor function and have a significantly shortened lifespan.
Connell-Crowley
Lisa
L
Basic Neuroscience Program, National Institute of Neurological Disorders and Stroke (NINDS), National Human Genome Research Institute (NHGRI), National Institutes of Health Bldg 37, Rm 1016, 37 Convent Drive, Bethesda, MD 20892, USA.
Vo
Duc
D
Luke
Lori
L
Giniger
Edward
E
D000367:Age Factors; D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000648:ultrastructure; D001522:Behavior, Animal; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D005260:Female; D017344:Genes, Insect; D008136:Longevity; D008297:Male; D009046:Motor Neurons / Q000502:physiology; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; C089495:neuronal Cdk5 activator (p25-p35); D051360:Cyclin-Dependent Kinase 5; C495904:Cdk5 protein, Drosophila