The receptor protein tyrosine phosphatase HmLAR1 is up-regulated in the CNS of the adult medicinal leech following injury and is required for neuronal sprouting and regeneration

Sethi, Jasmine; Zhao, Bailey; Cuvillier-Hot, Virginie; Boidin-Wichlacz, Céline; Macagno, Eduardo R.; Baker, Maureen

doi:10.1016/j.mcn.2010.08.002

Cited by 8 publications

(5 citation statements)

References 55 publications

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“…For control injections, a Xenopus elongation factor template was used which encompasses a 440 bp fragment and is supplied with the kit. Intracellular siRNA injections into the Rz neurons were performed using pressure injection as described elsewhere (Sethi et al, ). RNAi knockdown was performed on intact leech embryos at E13‐E14.…”

Section: Methodsmentioning

confidence: 99%

Purinergic modulation of neuronal gap junction circuits in the CNS of the leech

Segura

Abdulnoor

Hua

et al. 2020

J of Neuroscience Research

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Gap junctions (GJs) are widely distributed in brains across the animal kingdom. To visualize the GJ-coupled networks of two major mechanosensory neurons in the ganglia of medicinal leeches, we injected these cells with the GJ-permeable tracer Neurobiotin. When diffusion time was limited to only 30 min, tracer coupling was highly variable for both cells, suggesting a possible modulation of GJ permeability. In invertebrates the innexins (homologs of vertebrate pannexins) form the GJs.Because extracellular adenosine triphosphate (ATP) modulates pannexin and leech innexin hemichannel permeability and is released by leech glial cells following injury, we tested the effects of bath application of ATP after the injection of Neurobiotin and observed a significant increase in the number of neurons tracer coupled to the sensory neurons. This effect required the elevation of intracellular Ca 2+ and could be produced by bath application of caffeine. Conversely, scavenging endogenous extracellular ATP with the ATPase apyrase decreased the number of coupled cells.ATP also increased electrical conductance and tracer permeability between the bilateral Retzius neurons. This modulatory effect of ATP on GJ coupling was blocked by siRNA knockdown of a P1-like adenosine receptor. Finally, exposure of leech ganglia to extracellular ATP induced a characteristic low frequency (<0.3 Hz) rhythmic bursting activity that was roughly synchronous among multiple neurons, a behavior that was significantly attenuated by the GJ blocker octanol. These findings highlight the mediation by ATP of a robust physiological mechanism for modifying neuronal circuits by rapidly recruiting neurons into active networks and entraining synchronized bursting activity.

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Section: Methodsmentioning

confidence: 99%

Purinergic modulation of neuronal gap junction circuits in the CNS of the leech

Segura

Abdulnoor

Hua

et al. 2020

J of Neuroscience Research

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“…RNA was extracted and mRNA was purified from single identified adult neurons [Retzius (RZ), Anterior Pagoda (AP), and Pressure (P) cells)] as described in Sethi et al (2010). For each type of neuron, a minimum of three cells were taken and run with each gene of interest.…”

Section: Characterizing Innexins Present In Single Neuronsmentioning

confidence: 99%

The medicinal leech genome encodes 21 innexin genes: different combinations are expressed by identified central neurons

Kandarian

Sethi

et al. 2012

Dev Genes Evol

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Gap junctional proteins are important components of signaling pathways required for the development and ongoing functions of all animal tissues, particularly the nervous system, where they function in the intracellular and extracellular exchange of small signaling factors and ions. In animals whose genomes have been sufficiently sequenced, large families of these proteins, connexins, pannexins, and innexins, have been found, with 25 innexins in the nematode Caenorhabditis elegans Starich et al. (Cell Commun Adhes 8: 311-314, 2001) and at least 37 connexins in the zebrafish Danio rerio Cruciani and Mikalsen (Biol Chem 388:253-264, 2009). Having recently sequenced the medicinal leech Hirudo verbana genome, we now report the presence of 21 innexin genes in this species, nine more than we had previously reported from the analysis of an EST-derived transcriptomic database Dykes and Macagno (Dev Genes Evol 216: 185-97, 2006); Macagno et al. (BMC Genomics 25:407, 2010). Gene structure analyses show that, depending on the leech innexin gene, they can contain from 0 to 6 introns, with closely related paralogs showing the same number of introns. Phylogenetic trees comparing Hirudo to another distantly related leech species, Helobdella robusta, shows a high degree of orthology, whereas comparison to other annelids shows a relatively low level. Comparisons with other Lophotrochozoans, Ecdyzozoans and with vertebrate pannexins suggest a low number (one to two) of ancestral innexin/pannexins at the protostome/deuterostome split. Whole-mount in situ hybridization for individual genes in early embryos shows that ∼50% of the expressed innexins are detectable in multiple tissues. Expression analyses using quantitative PCR show that ∼70% of the Hirudo innexins are expressed in the nervous system, with most of these detected in early development. Finally, quantitative PCR analysis of several identified adult neurons detects the presence of different combinations of innexin genes, a property that may underlie the participation of these neurons in different adult coupling circuits.

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“…Here we discover a new player in the mechanism that maintains GSCs in their niche in Drosophila testes: the receptor tyrosine phosphatase Leukocyte-antigen-related-like (Lar), which is best known for its role in axonal migration, target selection and synapse formation in the nervous system Chagnon et al, 2004;Johnson and Van Vactor, 2003;Sethi et al, 2010). Drosophila Lar is a transmembrane type IIA receptor protein tyrosine phosphatase that contains N-terminal immunoglobulin-like domains and membrane-proximal fibronectin type III repeats in its extracellular region, a single-pass transmembrane domain and two tandem repeats of protein tyrosine phosphatase domains in its cytoplasmic region (Chagnon et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

The receptor tyrosine phosphatase Lar regulates adhesion between Drosophila male germline stem cells and the niche

2012

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SUMMARYThe stem cell niche provides a supportive microenvironment to maintain adult stem cells in their undifferentiated state. Adhesion between adult stem cells and niche cells or the local basement membrane ensures retention of stem cells in the niche environment. Drosophila male germline stem cells (GSCs) attach to somatic hub cells, a component of their niche, through Ecadherin-mediated adherens junctions, and orient their centrosomes toward these localized junctional complexes to carry out asymmetric divisions. Here we show that the transmembrane receptor tyrosine phosphatase Leukocyte-antigen-related-like (Lar), which is best known for its function in axonal migration and synapse morphogenesis in the nervous system, helps maintain GSCs at the hub by promoting E-cadherin-based adhesion between hub cells and GSCs. Lar is expressed in GSCs and early spermatogonial cells and localizes to the hub-GSC interface. Loss of Lar function resulted in a reduced number of GSCs at the hub. Lar function was required cell-autonomously in germ cells for proper localization of Adenomatous polyposis coli 2 and Ecadherin at the hub-GSC interface and for the proper orientation of centrosomes in GSCs. Ultrastructural analysis revealed that in Lar mutants the adherens junctions between hub cells and GSCs lack the characteristic dense staining seen in wild-type controls. Thus, the Lar receptor tyrosine phosphatase appears to polarize and retain GSCs through maintenance of localized E-cadherinbased adherens junctions.

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The receptor protein tyrosine phosphatase HmLAR1 is up-regulated in the CNS of the adult medicinal leech following injury and is required for neuronal sprouting and regeneration

Cited by 8 publications

References 55 publications

Purinergic modulation of neuronal gap junction circuits in the CNS of the leech

Purinergic modulation of neuronal gap junction circuits in the CNS of the leech

The medicinal leech genome encodes 21 innexin genes: different combinations are expressed by identified central neurons

The receptor tyrosine phosphatase Lar regulates adhesion between Drosophila male germline stem cells and the niche

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