L1 is a transmembranal hornophilic cell adhesion molecule of the immunoglobulin superfamily expressed by neural and lymphoid cells. The heat‐stable antigen (HSA, murine CD24) nectadrin is a highly and heterogeneously glycosylated glycophosphatidylinositol‐linked differentiation antigen of haematopoietic and neural cells. L1 and nectadrin have been shown to mediate cell adhesion and intracellular Ca2+ signals in neurons and B lymphoblasts, respectively. Here we show that nectadrin is co‐expressed with L1 in murine cerebellar granule cell neurons and neuroblastoma N2A cells. Purified nectadrin bound to L1 with an apparent binding ratio of five nectadrin molecules to one L1 molecule at saturation. Binding between nectadrin and purified N‐CAM was not observed. In co‐capping experiments nectadrin co‐redistributed with L1 and N‐CAM. Since in these cells N‐CAM and L1 cohere by cis binding nectadrin appears to join the L1‐N‐CAM complex through binding to L1. Antibodies to each L1 and nectadrin evoked small increases in the intracellular Ca2+ concentration. However, when both antibodies were added together or in tandem to the cells, a strong intracellular Ca2+ signal was measured that was at least 6‐ and 10‐fold stronger than the signal separately induced by L1 and nectadrin antibodies respectively. Such a cooperative effect was not observed in B lymphoblasts, using the same antibodies, or in neurons, using a combination of L1 and Thy‐1 antibodies. Both the weak Ca2+ signal mediated by L1 alone and the enhanced signal jointly triggered by antibodies to L1 and nectadrin were inhibited by phorbol 12‐myristate 13‐acetate and were not significantly affected by Ni2+ and Cd2+ cations, suggesting that they are related to one another and involve recruitment of intracellular Ca2+. Nectadrin therefore appears to join a functional complex of neuronal adhesion molecules and to potentiate the signal transduction pathway of L1, possibly in response to neuron‐neuron contact formation.
|Original language||English (US)|
|Number of pages||12|
|Journal||European Journal of Neuroscience|
|State||Published - May 1995|
All Science Journal Classification (ASJC) codes
- nervous system
- signal transduction