Cell surface beta1,4-galactosyltransferase function in mammary gland morphogenesis: insights from transgenic and knockout mouse models.
Development and morphogenesis are profoundly influenced by cell-cell and cell-extracellular matrix (ECM) interactions that are governed by cell surface receptor association with specific ligands. One such receptor is the long isoform of beta1,4-galactosyltransferase I (GalT I), a small proportion of which is targeted to the plasma membrane. Surface-expressed GalT I binds to specific glycoside residues on multiple extracellular ligands, and GalT I binding to specific ligands mediates cell-cell as well as cell-matrix interactions for a variety of cells, including mammary epithelia. Significant insight into surface GalT I function in mammary gland development and morphogenesis has been gained through the analysis of mouse transgenic and knockout models of surface GalT I misexpression. Overexpression of cell surface GalT I leads to impaired lactation as a result of reduced branching and differentiation and elevated apoptosis, while deleting surface GalT I enhances branching and differentiation and reduces apoptosis. These phenotypes can be attributed in large part to altered cell-ECM interactions. The current and future challenges are to use these mouse models to dissect the molecular mechanisms that govern surface GalT I function as a receptor in the normal mammary gland, as well as to assess the potential for surface GalT I misexpression to contribute to disease.
Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131, USA. hhathaway@salud.unm.edu
Helen J
HJ
Hathaway
D000818:Animals; D008321:Mammary Glands, Animal / Q000254:growth & development* / Q000378:metabolism*; D051379:Mice; D023421:Models, Animal; D009024:Morphogenesis; D009237:N-Acetyllactosamine Synthase / Q000737:chemistry / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*
D009237:N-Acetyllactosamine Synthase