@article {68530, title = {Small molecule inhibitors of mammalian glycosylation.}, journal = {Matrix Biology Plus}, volume = {16}, year = {2022}, month = {2022 Mar 16}, pages = {100108}, abstract = {

Glycans are one of the fundamental biopolymers encountered in living systems. Compared to polynucleotide and polypeptide biosynthesis, polysaccharide biosynthesis is a uniquely combinatorial process to which interdependent enzymes with seemingly broad specificities contribute. The resulting intracellular cell surface, and secreted glycans play key roles in health and disease, from embryogenesis to cancer progression. The study and modulation of glycans in cell and organismal biology is aided by small molecule inhibitors of the enzymes involved in glycan biosynthesis. In this review, we survey the arsenal of currently available inhibitors, focusing on agents which have been independently validated in diverse systems. We highlight the utility of these inhibitors and drawbacks to their use, emphasizing the need for innovation for basic research as well as for therapeutic applications.

}, issn = {2590-0285}, doi = {10.1016/j.mbplus.2022.100108}, author = {Almahayni, Karim and Spiekermann, Malte and Fiore, Antonio and Yu, Guoqiang and Pedram, Kayvon and M{\"o}ckl, Leonhard} } @article {66014, title = {Physical Principles of Membrane Shape Regulation by the Glycocalyx}, journal = {Cell}, volume = {177}, year = {2019}, month = {Jan-06-2019}, pages = {1757 - 1770.e21}, abstract = {

Cells bend their plasma membranes into highly curved forms to interact with the local environment, but how shape generation is regulated is not fully resolved. Here, we report a synergy between shape-generating processes in the cell interior and the external organization and composition of the cell-surface\ glycocalyx.\ Mucinbiopolymers\ and long-chain\ polysaccharides\ within the glycocalyx can generate entropic forces that favor or disfavor the projection of spherical and finger-like extensions from the cell surface. A polymer brush model of the glycocalyx successfully predicts the effects of polymer size and cell-surface density on membrane morphologies. Specific glycocalyx compositions can also induce plasma membrane instabilities to generate more exotic undulating and pearled\ membrane structures\ and drive secretion of extracellular vesicles. Together, our results suggest a fundamental role for the glycocalyx in regulating curved membrane features that serve in communication between cells and with the\ extracellular matrix.

}, issn = {00928674}, doi = {10.1016/j.cell.2019.04.017}, url = {https://www.sciencedirect.com/science/article/pii/S0092867419304039?via\%3Dihub}, author = {Shurer, Carolyn R. and Kuo, Joe Chin-Hun and Roberts, LaDeidra Mon{\'e}t and Gandhi, Jay G. and Colville, Marshall J. and Enoki, Thais A. and Pan, Hao and Su, Jin and Noble, Jade M. and Hollander, Michael J. and O{\textquoteright}Donnell, John P. and Yin, Rose and Pedram, Kayvon and M{\"o}ckl, Leonhard and Kourkoutis, Lena F. and Moerner, W.E. and Bertozzi, Carolyn R. and Feigenson, Gerald W. and Reesink, Heidi L. and Paszek, Matthew J.} } @article {66013, title = {Quantitative Super-Resolution Microscopy of the Mammalian Glycocalyx}, journal = {Developmental Cell}, volume = {50}, year = {2019}, month = {Jan-07-2019}, pages = {57 - 72.e6}, abstract = {

The mammalian glycocalyx is a heavily glycosylated extramembrane compartment found on nearly every cell. Despite its relevance in both health and disease, studies of the glycocalyx remain hampered by a paucity of methods to spatially classify its components. We combine metabolic labeling, bioorthogonal chemistry, and super-resolution localization microscopy to image two constituents of cell-surface glycans,\ N-acetylgalactosamine (GalNAc) and sialic acid, with 10{\textendash}20\ nm precision in 2D and 3D. This approach enables two measurements: glycocalyx height and the distribution of individual sugars distal from the membrane. These measurements show that the glycocalyx exhibits nanoscale organization on both cell lines and primary human tumor cells. Additionally, we observe enhanced glycocalyx height in response to epithelial-to-mesenchymal transition and to oncogenic\ KRAS\ activation. In the latter case, we trace increased height to an effector gene,\ GALNT7. These data highlight the power of advanced imaging methods to provide molecular and functional insights into glycocalyx biology.

}, issn = {15345807}, doi = {10.1016/j.devcel.2019.04.035}, url = {https://www.sciencedirect.com/science/article/pii/S1534580719303326?via\%3Dihub}, author = {M{\"o}ckl, Leonhard and Pedram, Kayvon and Roy, Anish R. and Krishnan, Venkatesh and Gustavsson, Anna-Karin and Dorigo, Oliver and Bertozzi, Carolyn R. and Moerner, W.E.} }