A DROSOPHILA NEUREXIN IS REQUIRED FOR SEPTATE JUNCTION AND BLOOD-NERVE BARRIER FORMATION AND FUNCTION

Septate and tight junctions are thought to seal neighboring cells toge ther and to function as barriers between epithelial cells. We have cha racterized a novel member of the neurexin family, Neurexin IV (NRX), w hich is localized to septate junctions (SJs) of epithelial and glial c ells. NRX is a transmembrane protein with a cytoplasmic domain homolog ous to glycophorin C, a protein required for anchoring protein 4.1 in the red blood cell. Absence of NRX results in mislocalization of Corac le, a Drosophila protein 4.1 homolog, at SJs and causes dorsal closure defects similar to those observed in coracle mutants. nrx mutant embr yos are paralyzed, and electrophysiological studies indicate that the rack of NRX in glial-glial SJs causes a breakdown of the blood-brain b arrier. Electron microscopy demonstrates that nrx mutants lack the lad der-like intercellular septa characteristic of pleated SJs (pSJs). The se studies identify NRX as the first transmembrane protein of SJ and d emonstrate a requirement for NRX in the formation of septate-junction septa and intercellular barriers.