title: The receptor tyrosine phosphatase Lar regulates adhesion between Drosophila male germline stem cells and the niche.
abstract: The stem cell niche provides a supportive microenvironment to maintain adult stem cells in their undifferentiated state. Adhesion between adult stem cells and niche cells or the local basement membrane ensures retention of stem cells in the niche environment. Drosophila male germline stem cells (GSCs) attach to somatic hub cells, a component of their niche, through E-cadherin-mediated adherens junctions, and orient their centrosomes toward these localized junctional complexes to carry out asymmetric divisions. Here we show that the transmembrane receptor tyrosine phosphatase Leukocyte-antigen-related-like (Lar), which is best known for its function in axonal migration and synapse morphogenesis in the nervous system, helps maintain GSCs at the hub by promoting E-cadherin-based adhesion between hub cells and GSCs. Lar is expressed in GSCs and early spermatogonial cells and localizes to the hub-GSC interface. Loss of Lar function resulted in a reduced number of GSCs at the hub. Lar function was required cell-autonomously in germ cells for proper localization of Adenomatous polyposis coli 2 and E-cadherin at the hub-GSC interface and for the proper orientation of centrosomes in GSCs. Ultrastructural analysis revealed that in Lar mutants the adherens junctions between hub cells and GSCs lack the characteristic dense staining seen in wild-type controls. Thus, the Lar receptor tyrosine phosphatase appears to polarize and retain GSCs through maintenance of localized E-cadherin-based adherens junctions.
authors.affiliation: Department of Developmental Biology, Stanford University, School of Medicine, Stanford, CA 94305, USA.
authors.forename: Shrividhya
authors.initials: S
authors.lastname: Srinivasan
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Mahowald
authors.forename: Margaret T
authors.initials: MT
authors.lastname: Fuller
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D019070:Cell Lineage; D003433:Crosses, Genetic; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster; D005260:Female; D005854:Germ Cells / Q000166:cytology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008297:Male; D008858:Microscopy, Phase-Contrast / Q000379:methods; D054557:Receptor-Like Protein Tyrosine Phosphatases / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*
chemical_list: D015820:Cadherins; D029721:Drosophila Proteins; D049452:Green Fluorescent Proteins; C117978:Lar protein, Drosophila; D054557:Receptor-Like Protein Tyrosine Phosphatases