TY - JOUR
T1 - A Drosophila neurexin is required for septate junction and blood-nerve barrier formation and function
AU - Baumgartner, Stefan
AU - Littleton, J. Troy
AU - Broadie, Kendal
AU - Bhat, Manzoor A.
AU - Harbecke, Ruth
AU - Lengyel, Judith A.
AU - Chiquet-Ehrismann, Ruth
AU - Prokop, Andreas
AU - Bellen, Hugo J.
N1 - Funding Information:
We thank Doris Martin for technical assistance, Markus Noll for libraries, and Beth Ostermeyer for human nrx IV. We thank Richard Atkinson, Becky Scott, and Michael Macini for help with confocal microscopy. We thank Richard Atkinson, Kwang Choi, Kyung Cho, Karen Schulze, Mark Wu, and Artur Kania for suggestions. We thank Rick Fehon, Helen Benes, Todd Laverty, Kathy Matthews, and the Indiana Stock Center for fly strains. A. P. and K. B. thank Michael Bate, in whose laboratory their work was carried out, and A. P. thanks H. Skaer and N. J. Lane for discussions. This work was supported by an NIH training grant to J. T. L., an NIH grant (HD09948) to J. A. L, and an NIH grant to H. J. B. A. P. was funded by a Human Capital and Mobility Fellowship (European Union) and by a Fellowship from the Lloyd's of London Tercentenery Foundation. K. B. was a Research Fellow of Girton College, Cambridge, whose work was supported by the Wellcome Trust and an Alfred P. Sloan Fellowship. H. J. B. is an Associate Investigator of the Howard Hughes Medical Institute. Reprint requests should be sent to H. J. B.
PY - 1996/12/13
Y1 - 1996/12/13
N2 - Septate and tight junctions are thought to seal neighboring cells together and to function as barriers between epithelial cells. We have characterized a novel member of the neurexin family, Neurexin IV (NRX), which is localized to septate junctions (SJs) of epithelial and glial cells. NRX is a transmembrane protein with a cytoplasmic domain homologous to glycophorin C, a protein required for anchoring protein 4.1 in the red blood cell. Absence of NRX results in mislocalization of Coracle, a Drosophila protein 4.1 homolog, at SJs and causes dorsal closure defects similar to those observed in coracle mutants, nrx mutant embryos are paralyzed, and electrophysiological studies indicate that the lack of NRX in glial-glial SJs causes a breakdown of the blood-brain barrier. Electron microscopy demonstrates that nrx mutants lack the ladder-like intercellular septa characteristic of pleated SJs (pSJs). These studies identify NRX as the first transmembrane protein of SJ and demonstrate a requirement for NRX in the formation of septate-junction septa and intercellular barriers.
AB - Septate and tight junctions are thought to seal neighboring cells together and to function as barriers between epithelial cells. We have characterized a novel member of the neurexin family, Neurexin IV (NRX), which is localized to septate junctions (SJs) of epithelial and glial cells. NRX is a transmembrane protein with a cytoplasmic domain homologous to glycophorin C, a protein required for anchoring protein 4.1 in the red blood cell. Absence of NRX results in mislocalization of Coracle, a Drosophila protein 4.1 homolog, at SJs and causes dorsal closure defects similar to those observed in coracle mutants, nrx mutant embryos are paralyzed, and electrophysiological studies indicate that the lack of NRX in glial-glial SJs causes a breakdown of the blood-brain barrier. Electron microscopy demonstrates that nrx mutants lack the ladder-like intercellular septa characteristic of pleated SJs (pSJs). These studies identify NRX as the first transmembrane protein of SJ and demonstrate a requirement for NRX in the formation of septate-junction septa and intercellular barriers.
UR - http://www.scopus.com/inward/record.url?scp=0030582713&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030582713&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(00)81800-0
DO - 10.1016/S0092-8674(00)81800-0
M3 - Article
C2 - 8978610
AN - SCOPUS:0030582713
SN - 0092-8674
VL - 87
SP - 1059
EP - 1068
JO - Cell
JF - Cell
IS - 6
ER -