Neurotrophins, such as brain-derived neurotrophic factor (BDNF), are key neuronal regulators. The adapter protein SH2B1 is recruited to neurotrophin receptors, and has been shown to enhance neurotrophin signaling. Interestingly, SH2B1 has four alternatively spliced isoforms, although their differential effects on neuronal outgrowth and function were unknown. A new study by Christin Carter-Su and colleagues (Cote et al., 2022) examines SH2B1 isoforms in detail. Using an Sh2b1 knockout (KO) mouse strain, the authors show that KO primary hippocampal neurons exhibit decreased neurite length and complexity and BDNF-induced gene expression. Reintroduction of each isoform into KO neurons suggests that SH2B1δ enhances neurite complexity and length to a greater extent than the other isoforms. Moreover, some human obesity-associated SH2B1 variants impair the ability of SH2B1δ to increase neurite branching. Interestingly, whereas the α, β and γ isoforms localise in the cytoplasm and plasma membrane, SH2B1δ contains two highly basic regions in its unique C-terminal tail that cause SH2B1δ to localise primarily in nucleoli. Mutational analysis experiments reveal that nucleolar localisation is in fact required for SH2B1δ function, including maximisation of neurite complexity and BDNF-dependent gene expression. Overall, this work provides insight on how the different SH2B1 isoforms regulate neuronal structure and gene expression, highlighting the contribution of nucleolar location to these functions.
Unraveling the role of SH2B1 isoforms on neuronal morphogenesis
- Split-screen
- Views Icon Views
-
Article Versions Icon
Versions
- Version of Record 10 February 2022
- Share Icon Share
-
Tools Icon
Tools
- Search Site
Unraveling the role of SH2B1 isoforms on neuronal morphogenesis. J Cell Sci 1 February 2022; 135 (3): e135_e0303. doi:
Download citation file:
Advertisement
Cited by
Call for papers: Cell Biology of Motors
(update)-MotorCFPExtended.jpg?versionId=3964)
Journal of Cell Science is pleased to welcome submissions for consideration for an upcoming special issue, Cell Biology of Motors. The deadline for submitting articles has been extended to 30 August 2022.
Find out more about our preprint policies
-bioRxiv.jpg?versionId=3964)
Last year, 47% of the manuscripts published in Journal of Cell Science were posted as preprints on bioRxiv. You can find our preprint policies here.
Cell scientist to watch: Jeremy Carlton
(update)-CSTW.png?versionId=3964)
Journal of Cell Science caught up with Jeremy Carlton, who established his independent research group in 2012 at the Division of Cancer Studies, King's College London. His lab is currently seconded to the Francis Crick Institute and is investigating membrane and organelle remodelling during cell division. This year, he was awarded the Hooke Medal by the British Society for Cell Biology (BSCB).
The FocalPlane Network
-FocalPlaneNetwork.png?versionId=3964)
The FocalPlane Network is an international directory of researchers with microscopy expertise including developers, imaging scientists and bioimage analysts. It is designed to help you find speakers, committee members, reviewers and potential collaborators. Find out more about the FocalPlane Network.
The Corona Files
-Mole.png?versionId=3964)
“We were not ready for a pandemic, despite decades of warnings.”
Our resident insectivore, Mole, continues his latest series – The Corona Files. This time, Mole reflects on what we have learned from the pandemic.