Receptor protein tyrosine phosphatase σ binds to neurons in the adult mouse brain

Yi, Jae-Hyuk; Katagiri, Yasuhiro; Lourie, Jacob; Bangayan, Nathanael J.; Symes, Aviva J.; Geller, Herbert M.

doi:10.1016/j.expneurol.2014.02.007

Cited by 10 publications

(10 citation statements)

References 33 publications

(53 reference statements)

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“…Among CS GAGs, only CS-E exhibited high-affinity binding sites for RPTP. It is striking that CS-A and CS-C, the major components of CS GAGs in vivo, did not support the binding, consistent with our previous finding for RPTP (6,18). These data emphasize the importance of appreciating the sulfation pattern and sources of CS in interpreting biological data (19).…”

Section: Heparin-binding Sites In Rptpsupporting

confidence: 74%

Identification of novel binding sites for heparin in receptor protein-tyrosine phosphatase (RPTPσ): Implications for proteoglycan signaling

Katagiri

Morgan

Bangayan

et al. 2018

Journal of Biological Chemistry

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Receptor protein-tyrosine phosphatase RPTPσ has important functions in modulating neural development and regeneration. Compelling evidence suggests that both heparan sulfate (HS) and chondroitin sulfate (CS) glycosaminoglycans (GAGs) bind to a series of Lys residues located in the first Ig domain of RPTPσ. However, HS promotes and CS inhibits axonal growth. Mutation of these Lys residues abolished binding and signal transduction of RPTPσ to CS, whereas HS binding was reduced, and signaling persisted. This activity was mediated through novel heparin-binding sites identified in the juxtamembrane region. Although different functional outcomes of HS and CS have been previously attributed to the differential oligomeric state of RPTPσ upon GAG binding, we found that RPTPσ was clustered by both heparin and CS GAG rich in 4,6--disulfated disaccharide units. We propose an additional mechanism by which RPTPσ distinguishes between HS and CS through these novel binding sites.

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Section: Heparin-binding Sites In Rptpsupporting

confidence: 74%

Identification of novel binding sites for heparin in receptor protein-tyrosine phosphatase (RPTPσ): Implications for proteoglycan signaling

Katagiri

Morgan

Bangayan

et al. 2018

Journal of Biological Chemistry

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“…It is believed that four positively charged lysine residues in the first immunoglobulin domain of the RPTP receptor mediate the specific interaction with GAGs (345, 432) on both CS and HS molecules (FIGURE 8A) (10,432). Sulfation patterning additionally affects binding of specific CSPGs to RPTP.…”

Section: Chondroitin Sulfate Proteoglycan Receptor Discovery and Mmentioning

confidence: 99%

“…Due to the nature of electrostatic interactions, the bifunctional RPTP is likely to bind most strongly with CS-D and CS-E. Given that the latter of these molecules is highly upregulated after CNS injury (42,93,432), this makes the receptor a strong candidate to target in a treatment strategy (42,221). Importantly, the downstream effectors of the RPTP signaling pathway have yet to be identified, meaning that the mechanism through which CSPGs mediate inhibitory signaling is not yet fully elucidated.…”

Section: Chondroitin Sulfate Proteoglycan Receptor Discovery and Mmentioning

confidence: 99%

The Biology of Regeneration Failure and Success After Spinal Cord Injury

Tran

Warren

Silver

2018

Physiological Reviews

616

557

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Since no approved therapies to restore mobility and sensation following spinal cord injury (SCI) currently exist, a better understanding of the cellular and molecular mechanisms following SCI that compromise regeneration or neuroplasticity is needed to develop new strategies to promote axonal regrowth and restore function. Physical trauma to the spinal cord results in vascular disruption that, in turn, causes blood-spinal cord barrier rupture leading to hemorrhage and ischemia, followed by rampant local cell death. As subsequent edema and inflammation occur, neuronal and glial necrosis and apoptosis spread well beyond the initial site of impact, ultimately resolving into a cavity surrounded by glial/fibrotic scarring. The glial scar, which stabilizes the spread of secondary injury, also acts as a chronic, physical, and chemo-entrapping barrier that prevents axonal regeneration. Understanding the formative events in glial scarring helps guide strategies towards the development of potential therapies to enhance axon regeneration and functional recovery at both acute and chronic stages following SCI. This review will also discuss the perineuronal net and how chondroitin sulfate proteoglycans (CSPGs) deposited in both the glial scar and net impede axonal outgrowth at the level of the growth cone. We will end the review with a summary of current CSPG-targeting strategies that help to foster axonal regeneration, neuroplasticity/sprouting, and functional recovery following SCI.

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“…Although studies with primary neuronal cultures have shown that PTPσ impairs synapse formation in vitro, evidence has been lacking in vivo (Han et al, 2018). Notably, in a recent study using an AP-tagged fusion construct in mouse brain tissue slices, PTPσ interacted directly with neurons, and binding persisted even after CSPGs and HSPGs were enzymatically digested (Yi et al, 2014). Although it remains unclear whether PTPσ deficiency impairs regenerative synaptogenesis in vivo, it is possible that this may have contributed to the neuron loss observed in our model via trophic deprivation.…”

Section: Alternative Cell-autonomous Effectsmentioning

confidence: 99%

PTPσ Knockdown in Lampreys Impairs Reticulospinal Axon Regeneration and Neuronal Survival After Spinal Cord Injury

Rodemer

Zhang

Sinitsa

et al. 2020

Front. Cell. Neurosci.

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Traumatic spinal cord injury (SCI) results in persistent functional deficits due to the lack of axon regeneration within the mammalian CNS. After SCI, chondroitin sulfate proteoglycans (CSPGs) inhibit axon regrowth via putative interactions with the LAR-family protein tyrosine phosphatases, PTPσ and LAR, localized on the injured axon tips. Unlike mammals, the sea lamprey, Petromyzon marinus, robustly recovers locomotion after complete spinal cord transection (TX). Behavioral recovery is accompanied by heterogeneous yet predictable anatomical regeneration of the lamprey's reticulospinal (RS) system. The identified RS neurons can be categorized as "good" or "bad" regenerators based on the likelihood that their axons will regenerate. Those neurons that fail to regenerate their axons undergo a delayed form of caspase-mediated cell death. Previously, this lab reported that lamprey PTPσ mRNA is selectively expressed in "bad regenerator" RS neurons, preceding SCI-induced caspase activation. Consequently, we hypothesized that PTPσ deletion would reduce retrograde cell death and promote axon regeneration. Using antisense morpholino oligomers (MOs), we knocked down PTPσ expression after TX and assessed the effects on axon regeneration, caspase activation, intracellular signaling, and behavioral recovery. Unexpectedly, PTPσ knockdown significantly impaired RS axon regeneration at 10 weeks post-TX, primarily due to reduced long-term neuron survival. Interestingly, cell loss was not preceded by an increase in caspase or p53 activation. Behavioral recovery was largely unaffected, although PTPσ knockdowns showed mild deficits in the recovery of swimming distance and latency to immobility during open field swim assays. Although the mechanism underlying the cell death following TX and PTPσ knockdown remains unknown, this study suggests that PTPσ is not a net negative regulator of long tract axon regeneration in lampreys.

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Receptor protein tyrosine phosphatase σ binds to neurons in the adult mouse brain

Cited by 10 publications

References 33 publications

Identification of novel binding sites for heparin in receptor protein-tyrosine phosphatase (RPTPσ): Implications for proteoglycan signaling

Identification of novel binding sites for heparin in receptor protein-tyrosine phosphatase (RPTPσ): Implications for proteoglycan signaling

The Biology of Regeneration Failure and Success After Spinal Cord Injury

PTPσ Knockdown in Lampreys Impairs Reticulospinal Axon Regeneration and Neuronal Survival After Spinal Cord Injury

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