8fn9
Crystal structure of the C-terminal Fg domain of TNR with the single FN domain of PTPRZCrystal structure of the C-terminal Fg domain of TNR with the single FN domain of PTPRZ
Structural highlights
DiseaseTENR_HUMAN The disease is caused by variants affecting the gene represented in this entry. FunctionTENR_HUMAN Neural extracellular matrix (ECM) protein involved in interactions with different cells and matrix components. These interactions can influence cellular behavior by either evoking a stable adhesion and differentiation, or repulsion and inhibition of neurite growth. Binding to cell surface gangliosides inhibits RGD-dependent integrin-mediated cell adhesion and results in an inhibition of PTK2/FAK1 (FAK) phosphorylation and cell detachment. Binding to membrane surface sulfatides results in a oligodendrocyte adhesion and differentiation. Interaction with CNTN1 induces a repulsion of neurons and an inhibition of neurite outgrowth. Interacts with SCN2B may play a crucial role in clustering and regulation of activity of sodium channels at nodes of Ranvier. TNR-linked chondroitin sulfate glycosaminoglycans are involved in the interaction with FN1 and mediate inhibition of cell adhesion and neurite outgrowth. The highly regulated addition of sulfated carbohydrate structure may modulate the adhesive properties of TNR over the course of development and during synapse maintenance (By similarity). 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 Jun 23:104952. doi: 10.1016/j.jbc.2023.104952. PMID:37356715[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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