cAMP-dependent phosphorylation of Aplysia twitchin may mediate modulation of muscle contractions by neuropeptide cotransmitters.
Acting through a cAMP-cAMP-dependent protein kinase (cAPK) cascade, members of two neuropeptide families, the small cardioactive peptides and myomodulins, modulate contraction amplitude and relaxation rate in the accessory radula closer (ARC) muscle of the marine mollusc Aplysia californica. An approximately 750-kDa phosphoprotein was identified in the ARC muscle as the major substrate for cAPK activated either by application of neuropeptides or by peptides released by motorneuron stimulation at physiological frequencies. Immunoblot and immunoelectron microscopy experiments revealed the widespread presence of this protein in Aplysia muscles and its colocalization with contractile filaments in the ARC muscle. Sequence analysis of proteolytic peptide fragments derived from the protein indicated that it is structurally related to the muscle protein twitchin. Finally, the level of neuropeptide-induced phosphorylation of the protein correlated well with peptidergic modulation of the relaxation rate of the muscle. We propose that twitchin in Aplysia, and perhaps in other species, may mediate the modulation of the relaxation rate of muscle contractions.
Probst
W C
WC
Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, NY 10029.
Cropper
E C
EC
Heierhorst
J
J
Hooper
S L
SL
Jaffe
H
H
Vilim
F
F
Beushausen
S
S
Kupfermann
I
I
Weiss
K R
KR
D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia; D001483:Base Sequence; D029742:Caenorhabditis elegans Proteins; D002148:Calmodulin-Binding Proteins; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D015801:Helminth Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009119:Muscle Contraction; D009124:Muscle Proteins / Q000378:metabolism*; D009126:Muscle Relaxation; D009469:Neuromuscular Junction / Q000502:physiology; D009479:Neuropeptides / Q000502:physiology; D010766:Phosphorylation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D009435:Synaptic Transmission
D029742:Caenorhabditis elegans Proteins; D002148:Calmodulin-Binding Proteins; D015801:Helminth Proteins; D009124:Muscle Proteins; D009479:Neuropeptides; C489233:unc-22 protein, C elegans; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases