| First Author | Cote JL | Year | 2022 |
| Journal | J Cell Sci | Volume | 135 |
| Issue | 3 | PubMed ID | 35019135 |
| Mgi Jnum | J:354475 | Mgi Id | MGI:7278950 |
| Doi | 10.1242/jcs.259179 | Citation | Cote JL, et al. (2022) The nucleolar delta isoform of adapter protein SH2B1 enhances morphological complexity and function of cultured neurons. J Cell Sci 135(3):jcs259179 |
| abstractText | The adapter protein SH2B1 is recruited to neurotrophin receptors, including TrkB (also known as NTRK2), the receptor for brain-derived neurotrophic factor (BDNF). Herein, we demonstrate that the four alternatively spliced isoforms of SH2B1 (SH2B1alpha-SH2B1delta) are important determinants of neuronal architecture and neurotrophin-induced gene expression. Primary hippocampal neurons from Sh2b1-/- [knockout (KO)] mice exhibit decreased neurite complexity and length, and BDNF-induced expression of the synapse-related immediate early genes Egr1 and Arc. Reintroduction of each SH2B1 isoform into KO neurons increases neurite complexity; the brain-specific delta isoform also increases total neurite length. Human obesity-associated variants, when expressed in SH2B1delta, alter neurite complexity, suggesting that a decrease or increase in neurite branching may have deleterious effects that contribute to the severe childhood obesity and neurobehavioral abnormalities associated with these variants. Surprisingly, in contrast to SH2B1alpha, SH2B1beta and SH2B1gamma, which localize primarily in the cytoplasm and plasma membrane, SH2B1delta resides primarily in nucleoli. Some SH2B1delta is also present in the plasma membrane and nucleus. Nucleolar localization, driven by two highly basic regions unique to SH2B1delta, is required for SH2B1delta to maximally increase neurite complexity and BDNF-induced expression of Egr1, Arc and FosL1. |
