8fnb | pdb_00008fnb
Crystal structure of the C-terminal Fg domain of human TNC with the mutations Y2140H and S2164H
Structural highlights
FunctionTENA_HUMAN Extracellular matrix protein implicated in guidance of migrating neurons as well as axons during development, synaptic plasticity as well as neuronal regeneration. Promotes neurite outgrowth from cortical neurons grown on a monolayer of astrocytes. Ligand for integrins alpha-8/beta-1, alpha-9/beta-1, alpha-V/beta-3 and alpha-V/beta-6. Publication Abstract from PubMedNeural plasticity, the ability to alter the structure and function of neural circuits, varies throughout the age of an individual. The end of the hyperplastic period in the central nervous system coincides with the appearance of honeycomb-like structures called perineuronal nets (PNNs) that surround a subset of neurons. PNNs are a condensed form of neural extracellular matrix that include the glycosaminoglycan hyaluronan and extracellular matrix proteins such as aggrecan and tenascin-R (TNR). PNNs are key regulators of developmental neural plasticity and cognitive functions, yet our current understanding of the molecular interactions that help assemble them remains limited. Disruption of Ptprz1, the gene encoding the receptor protein tyrosine phosphatase RPTPzeta, altered the appearance of nets from a reticulated structure to puncta on the surface of cortical neuron bodies in adult mice. The structural alterations mirror those found in Tnr(-/-) mice, and TNR is absent from the net structures that form in dissociated cultures of Ptprz1(-/-) cortical neurons. These findings raised the possibility that TNR and RPTPzeta cooperate to promote the assembly of PNNs. Here, we show that TNR associates with the RPTPzeta ectodomain and provide a structural basis for these interactions. Furthermore, we show that RPTPzeta forms an identical complex with tenascin-C, a homolog of TNR that also regulates neural plasticity. Finally, we demonstrate that mutating residues at the RPTPzeta-TNR interface impairs the formation of PNNs in dissociated neuronal cultures. Overall, this work sets the stage for analyzing the roles of protein-protein interactions that underpin the formation of nets. Protein-protein interactions between tenascin-R and RPTPzeta/phosphacan are critical to maintain the architecture of perineuronal nets.,Sinha A, Kawakami J, Cole KS, Ladutska A, Nguyen MY, Zalmai MS, Holder BL, Broerman VM, Matthews RT, Bouyain S J Biol Chem. 2023 Aug;299(8):104952. doi: 10.1016/j.jbc.2023.104952. Epub 2023 , Jun 23. PMID:37356715[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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