ANALYSIS OF THE ROLE OF CALMODULIN-BINDING AND SEQUESTRATION IN NEUROMODULIN (GA1-43) FUNCTION

We demonstrated previously that forced expression of the neuronal phos phoprotein neuromodulin (also known as GAP-43, F1, B-50, and p57) in m ouse anterior pituitary AtT-20 cells enhances depolarization mediated. secretion and alters cellular morphology. Here we analyze the role of calmodulin binding by neuromodulin in these responses, In cells expre ssing mild-type neuromodulin, a complex with calmodulin that is sensit ive to intracellular calcium and phosphorylation is localized to the p lasma membrane, Transfection of several mutant forms of neuromodulin s hows that the effects of this protein on secretion are dependent on bo th calmodulin binding and association with the plasma membrane, In con trast, the morphological changes depend only oh membrane association. Thus, the multitude of effects of neuromodulin noted in previous studi es may result from divergent properties of this protein.