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.