{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:23:20Z","timestamp":1791145400887,"version":"4.1.0"},"reference-count":70,"publisher":"The Company of Biologists","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,2,15]]},"abstract":"<jats:p>The vulval precursor cells (VPCs) of Caenorhabditis elegans are polarized epithelial cells that adopt a precise pattern of fates through regulated activity of basolateral LET-23\/EGF receptor and apical LIN-12\/Notch. During VPC patterning, there is reciprocal modulation of endocytosis and trafficking of both LET-23 and LIN-12. We identified sel-2 as a negative regulator of lin-12\/Notch activity in the VPCs, and found that SEL-2 is the homolog of two closely related human proteins, neurobeachin(also known as BCL8B) and LPS-responsive, beige-like anchor protein (LRBA). SEL-2, neurobeachin and LRBA belong to a distinct subfamily of BEACH-WD40 domain-containing proteins. Loss of sel-2 activity leads to basolateral mislocalization and increased accumulation of LIN-12 in VPCs in which LET-23 is not active, and to impaired downregulation of basolateral LET-23 in VPCs in which LIN-12 is active. Downregulation of apical LIN-12 in the VPC in which LET-23 is active is not affected. In addition, in sel-2 mutants, the polarized cells of the intestinal epithelium display an aberrant accumulation of the lipophilic dye FM4-64 when the dye is presented to the basolateral surface. Our observations indicate that SEL-2\/neurobeachin\/LRBA is involved in endosomal traffic and may be involved in efficient delivery of cell surface proteins to the lysosome. Our results also suggest that sel-2 activity may contribute to the appropriate steady-state level of LIN-12 or to trafficking events that affect receptor activation.<\/jats:p>","DOI":"10.1242\/dev.02767","type":"journal-article","created":{"date-parts":[[2007,1,11]],"date-time":"2007-01-11T01:26:44Z","timestamp":1168478804000},"page":"691-702","source":"Crossref","is-referenced-by-count":59,"title":["SEL-2, the<i>C. elegans<\/i>neurobeachin\/LRBA homolog, is a negative regulator of<i>lin-12\/Notch<\/i>activity and affects endosomal traffic in polarized epithelial cells"],"prefix":"10.1242","volume":"134","author":[{"given":"Natalie","family":"de Souza","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, 701 W. 168th Street, Hammer Health Sciences, New York, NY 10032,USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura G.","family":"Vallier","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, 701 W. 168th Street, Hammer Health Sciences, New York, NY 10032,USA."},{"name":"Department of Biology, Hofstra University, Gittleson Hall Room 103, Hempstead,NY 11549, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Fares","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, 701 W. 168th Street, Hammer Health Sciences, New York, NY 10032,USA."},{"name":"Department of Molecular and Cellular Biology, University of Arizona, Life Sciences South, Room 531, 1007 E. Lowell Street, Tucson, AZ 85721, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iva","family":"Greenwald","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, 701 W. 168th Street, Hammer Health Sciences, New York, NY 10032,USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042612261768100_REF1","doi-asserted-by":"crossref","unstructured":"Bettinger, J. C., Lee, K. and Rougvie, A. E.(1996). Stage-specific accumulation of the terminal differentiation factor LIN-29 during Caenorhabditis elegans development. Development122,2517-2527.","DOI":"10.1242\/dev.122.8.2517"},{"key":"2021042612261768100_REF2","doi-asserted-by":"crossref","unstructured":"Bonifacino, J. S. and Rojas, R. (2006). Retrograde transport from endosomes to the trans-Golgi network. Nat. Rev. Mol. 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