Robert O'Leary's research while affiliated with Icahn School of Medicine at Mount Sinai and other places
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Publications (3)
Differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes is regulated by the interplay between extrinsic signals and intrinsic epigenetic determinants. In this study, we analyze the effect that the extracellular ligands sonic hedgehog (Shh) and bone morphogenetic protein 4 (BMP4), have on histone acetylation and gene...
Clustered protocadherins (Pcdhs) are arranged in gene clusters (α, β, and γ) with variable and constant exons. Variable exons encode cadherin and transmembrane domains and ~90 cytoplasmic residues. The 14 Pcdh-αs and 22 Pcdh-γs are spliced to constant exons, which, for Pcdh-γs, encode ~120 residues of an identical cytoplasmic moiety. Pcdh-γs partic...
Gamma protocadherins (Pcdh-γs) resemble classical cadherins and have the potential to engage in cell-cell interactions with homophilic properties. Emerging evidence suggests non-conventional roles for some protocadherins in neural development. We sought to determine whether Pcdh-γ trafficking in neurons is consistent with an intracellular role for...
Citations
... During CNS development, multiple morphogen signaling domains can overlap and interplay to trigger cellular responses. For instance, Shh activity can be modulated by FGF, Wnt, or BMP but this crosstalk mainly relies on pathway transduction mechanisms rather than on modification of Shh gradient distribution [23][24][25][26][27][28][29][30]. In the context of the establishment of the Shh gradient itself, it is critical to understand how Shh protein is secreted and, more importantly, transported to induce many processes at long ranges. ...
... While Keeler et al. (2015) found that the C-terminal motif interacts with phosphatidyl inositol phospholipids (but not lysophospholipids or sphingolipids) and that PKC phosphorylation of S119 abrogates this binding, there are no data yet on the functional role this plays. One possible role could be in regulating g-Pcdh protein trafficking, given that removal of the cytoplasmic domain has been observed to increase cell surface expression, likely due to removal of ER-retention signals (Fernandez-Monreal et al., 2009;Hanson et al., 2010;O'Leary et al., 2011;Schreiner & Weiner, 2010;Thu et al., 2014). Several other studies have shown that a portion of g-Pcdh protein is associated with membrane vesicles of the endolysosome system, specifically late endosomes Phillips et al., 2003). ...
... These results in cell culture agree well with the observed distribution of endogenous Pcdhs in apparently similar compartments in cultured neurons and tissue in vivo (Phillips et al., 2003;Fernández-Monreal et al., 2010;LaMassa et al., 2021). In particular, Pcdh-γs were found in dendrites and spine compartments but their role in these locations in terms of synaptic function remain unknown. ...