LIMBIC SYSTEM-ASSOCIATED MEMBRANE-PROTEIN (LAMP) INDUCES NEURITE OUTGROWTH AND INTRACELLULAR CA2+ INCREASE IN PRIMARY FETAL NEURONS

The ability of cell adhesion molecules (CAMs) to transduce cell surfac e signals into intracellular responses is critical for developing neur ons, particularly during axonal pathfinding and targeting. It has been suggested that different CAMs can promote neuronal outgrowth via acti vation of common neuronal CAM-specific second-messenger pathways, alth ough the elements involved in this cascade could differ. Limbic system -associated membrane protein (LAMP), a member of the Ig superfamily, i s a molecule that promotes cell adhesion and neurite outgrowth from sp ecific populations of fetal neurons. In the present study, we show tha t LAMP can induce several types of calcium (Ca2+) signals. Neurite out growth is promoted if fetal hippocampal neurons are grown on lamp-tran sfected CHO cells. This LAMP-induced outgrowth of neurons is mediated in part through activation of L-type Ca channels. Application of solub le LAMP to cultures of fetal hippocampal neurons caused a sustained (u p to 60 min) elevation of intracellular Ca2+ as measured by fluo-3 flu orescence on a confocal microscope. The number of responding hippocamp al neurons was initially low, but increased with age in culture and th e [Ca2+](i) elevation was only partially decreased by an L-type Ca2+-c hannel blocker. In contrast, at all times in culture, only a small fra ction of neurons from visual cortex responded to LAMP application and only with transient elevation of cytosolic Ca2+ (<15 min). Based on th ese observations, LAMP appears to function primarily through hemophili c interactions and acts in part by modulating intracellular Ca2+ level s during neurite outgrowth by increasing the Ca2+ influx through L-typ e calcium channels, but has additional effects on intracellular Ca2+ s ignaling at later developmental stages.