The calmodulin antagonist W-7 affects transcytosis, lysosomal transport, and recycling but not endocytosis.
Calmodulin is a ubiquitous calcium-binding protein involved in the regulation of a variety of calcium-dependent cell functions. The present study provides evidence for a role of calmodulin in several steps of membrane transport along the endocytic pathway. Treatment of Madin-Darby canine kidney cells expressing the polymeric immunoglobulin receptor or a macrophage IgG Fc receptor with the calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7) inhibited their ability to mediate transcytosis of dimeric IgA or lysosomal degradation of immune complexes, respectively. Since both pathways rely on intact microtubules, the inhibitory effect of W-7 may reflect an effect on calmodulin-regulated microtubule function. However, although W-7 did not affect endocytosis, the drug also inhibited recycling of receptors from apical or basolateral endosomes back to the respective surfaces. Thus, calmodulin may regulate microtubule-dependent and independent endocytic membrane transport pathways.
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
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Hunziker
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000187:drug effects*; D007070:Immunoglobulin A / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects* / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D011961:Receptors, Fc / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology*; D014168:Transferrin / Q000378:metabolism
D002147:Calmodulin; D007070:Immunoglobulin A; D011961:Receptors, Fc; D013449:Sulfonamides; D014168:Transferrin; C017967:W 7