Elucidating the role

Posted by / 07-Feb-2020 01:13

Elucidating the role

O-Glc NAc glycosylation is a dynamic, inducible post-translational modification (PTM) essential for neuronal homeostasis and found on proteins associated with neurodegenerative diseases such as α-synuclein, amyloid precursor protein, and tau.Intracellularly, O-Glc NAc modification is cycled by two enzymes in mammalian cells: O-Glc NAc transferase (OGT) appends O-Glc NAc to serine or threonine residues and O-Glc NAcase (OGA) removes O-Glc NAc.To further complicate matters, several lysosomal and autophagic components are utilized during these processes, but it is unclear what delineates the specificity of their regulation.To help elucidate these mechanisms, our laboratory conducted a genome-wide si RNA screen, which identified several novel regulators of melanogenesis.Using WGCNA, we demonstrated that CREB O-Glc NAcylation at serine 40 and phosphorylation at serine 133 mediate mutually exclusive gene networks.The glycosylation-deficient mutant enhanced neuronal activity- and excitotoxicity-related gene networks while the phosphorylation-deficient mutant perturbed neuronal differentiation and amino and fatty acid metabolism-related gene networks.

We developed an improved approach to quantitatively label and enrich O-Glc NAcylated proteins for site identification.

Here, we established and employed biological and chemical tools to illuminate the role of O-Glc NAc in neuronal function.

In Chapter 2, we sought to determine the role of O-Glc NAc in learning, memory, and neurodegeneration.

A mechanistic rationalization is given for how asymmetric amplification is induced with fidelity in the Soai autocatalytic reaction by chiral initiators that are enantiomeric only by virtue of an isotope, e.g. Selectivity in formation of the product-initiator complex ultimately induces a slight enantioenrichment in the active dimer catalysts that trigger and direct the autocatalytic pathway.

A transient inhibition of the autocatalytic pathway at the outset of the reaction implicates an interaction between initiator and product initially formed in the uncatalyzed background reaction.

elucidating the role-2elucidating the role-68elucidating the role-14

Deletion of the OGT gene causes early postnatal lethality in mice, complicating efforts to study O-Glc NAc glycosylation in mature neuronal function and dysfunction.

One thought on “elucidating the role”