Adrenal chromaffin cells exhibit impaired granule trafficking in NCAM knockout mice.
Neural cell adhesion molecule (NCAM) plays several critical roles in neuron path-finding and intercellular communication during development. In the clinical setting, serum NCAM levels are altered in both schizophrenic and autistic patients. NCAM knockout mice have been shown to exhibit deficits in neuronal functions including impaired hippocampal long term potentiation and motor coordination. Recent studies in NCAM null mice have indicated that synaptic vesicle trafficking and active zone targeting are impaired, resulting in periodic synaptic transmission failure under repetitive physiological stimulation. In this study, we tested whether NCAM plays a role in vesicle trafficking that is limited to the neuromuscular junction or whether it may also play a more general role in transmitter release from other cell systems. We tested catecholamine release from neuroendocrine chromaffin cells in the mouse adrenal tissue slice preparation. We utilize electrophysiological and electrochemical measures to assay granule recruitment and targeting in wild-type and NCAM -/- mice. Our data show that NCAM -/- mice exhibit deficits in normal granule trafficking between the readily releasable pool and the highly release-competent immediately releasable pool. This defect results in a decreased rate of granule fusion and thus catecholamine release under physiological stimulation. Our data indicate that NCAM plays a basic role in the transmitter release mechanism in neuroendocrine cells through mediation of granule recruitment and is not limited to the neuromuscular junction and central synapse active zones.
Chan
Shyue-An
SA
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106-4970, USA.
Polo-Parada
Luis
L
Landmesser
Lynn T
LT
Smith
Corey
C
D000313:Adrenal Medulla / Q000166:cytology*; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism*; D002837:Chromaffin Granules / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D004563:Electrochemistry / Q000379:methods; D005089:Exocytosis / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000235:genetics; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry / Q000172:deficiency*; D050765:Qa-SNARE Proteins; D013572:Synaptic Vesicles / Q000502:physiology; D050825:Synaptosomal-Associated Protein 25; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection / Q000379:methods
D002395:Catecholamines; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D050765:Qa-SNARE Proteins; C494209:Snap25 protein, mouse; D050825:Synaptosomal-Associated Protein 25; C103912:Unc13a protein, rat; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium