2019 Highlights

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October 15, 2019

Volume 12, Issue 603

Tuning the regulator: Phosphorylation of KCC2 at two specific sites is critical for neurodevelopment

The K+/Cl− cotransporter KCC2 is a molecular switch between excitatory and inhibitory effects of GABAergic inputs into neurons. In a pair of exciting studies, Watanabe et al. and Pisella et al. elucidate the role of KCC2 dephosphorylation in this process and reveal its consequences...

ScienceSignaling.gif

October 15, 2019

Volume 12, Issue 603

Impaired regulation of KCC2 phosphorylation leads to neuronal network dysfunction and neurodevelopmental pathology

High intracellular concentrations of Cl− ions in neurons interfere with synaptic signaling, particularly of the inhibitory neurotransmitter of the central nervous system (CNS), γ-aminobutyric acid (GABA), and are implicated in several neurological diseases, such as epilepsy and schizophrenia...

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April 2019

Volume 25, Issue 4

EphrinB2-EphB4-RASA1 Signaling in Human Cerebrovascular Development and Disease

Genetic and functional studies in model organisms have revealed the importance of ephrinB2-EphB4-RASA1 signaling in multiple aspects of cerebrovascular development.
Recent whole exome sequencing studies in humans have identified mutations in EFNB2, EPHB4, and RASA1 in...

2019

Panchagnula S, Sularz AK, Kahle KT. Familial Trigeminal Neuralgia Cases Implicate Genetic Factors in Disease Pathogenesis. JAMA Neurol. 2019 Jan 1;76(1):9-10. doi: 10.1001/jamaneurol.2018.3322. PubMed PMID: 30398541.
Duran D, Zeng X, Jin SC, Choi J, Nelson-Williams C, Yatsula B, Gaillard J, Furey CG, Lu Q, Timberlake AT, Dong W, Sorscher MA, Loring E, Klein J, Allocco A, Hunt A, Conine S, Karimy JK, Youngblood MW, Zhang J, DiLuna ML, Matouk CC, Mane S, Tikhonova IR, Castaldi C, López-Giráldez F, Knight J, Haider S, Soban M, Alper SL, Komiyama M, Ducruet AF, Zabramski JM, Dardik A, Walcott BP, Stapleton CJ, Aagaard-Kienitz B, Rodesch G, Jackson E, Smith ER, Orbach DB, Berenstein A, Bilguvar K, Vikkula M, Gunel M, Lifton RP, Kahle KT. Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation. Neuron. 2019 Feb 6;101(3):429-443.e4. doi: 10.1016/j.neuron.2018.11.041. Epub 2018 Dec 18. PubMed PMID: 30578106.
Zeng X, Hunt A, Jin SC, Duran D, Gaillard J, Kahle KT. EphrinB2-EphB4-RASA1 Signaling in Human Cerebrovascular Development and Disease. Trends Mol Med. 2019 Apr;25(4):265-286. doi: 10.1016/j.molmed.2019.01.009. Epub 2019 Feb 25. Review. PubMed PMID: 30819650; PubMed Central PMCID: PMC6456402.
Duy PQ, Furey CG, Kahle KT. Trim71/lin-41 Links an Ancient miRNA Pathway to Human Congenital Hydrocephalus. Trends Mol Med. 2019 Jun;25(6):467-469. doi: 10.1016/j.molmed.2019.03.004. Epub 2019 Apr 8. PubMed PMID: 30975633.
Date P, Ackermann P, Furey C, Fink IB, Jonas S, Khokha MK, Kahle KT, Deniz E. Visualizing flow in an intact CSF network using optical coherence tomography: implications for human congenital hydrocephalus. Sci Rep. 2019 Apr 17;9(1):6196. doi: 10.1038/s41598-019-42549-4. PubMed PMID: 30996265; PubMed Central PMCID: PMC6470164.
Lalioti ME, Kaplani K, Lokka G, Georgomanolis T, Kyrousi C, Dong W, Dunbar A, Parlapani E, Damianidou E, Spassky N, Kahle KT, Papantonis A, Lygerou Z, Taraviras S. GemC1 is a critical switch for neural stem cell generation in the postnatal brain. Glia. 2019 Dec;67(12):2360-2373. doi: 10.1002/glia.23690. Epub 2019 Jul 22. PubMed PMID: 31328313.
Jin SC, Furey CG, Zeng X, Allocco A, Nelson-Williams C, Dong W, Karimy JK, Wang K, Ma S, Delpire E, Kahle KT. SLC12A ion transporter mutations in sporadic and familial human congenital hydrocephalus. Mol Genet Genomic Med. 2019 Sep;7(9):e892. doi: 10.1002/mgg3.892. Epub 2019 Aug 8. PubMed PMID: 31393094; PubMed Central PMCID: PMC6732308.
Pisella LI, Gaiarsa JL, Diabira D, Zhang J, Khalilov I, Duan J, Kahle KT, Medina I. Impaired regulation of KCC2 phosphorylation leads to neuronal network dysfunction and neurodevelopmental pathology. Sci Signal. 2019 Oct 15;12(603). pii: eaay0300. doi: 10.1126/scisignal.aay0300. PubMed PMID: 31615899.
Watanabe M, Zhang J, Mansuri MS, Duan J, Karimy JK, Delpire E, Alper SL, Lifton RP, Fukuda A, Kahle KT. Developmentally regulated KCC2 phosphorylation is essential for dynamic GABA-mediated inhibition and survival. Sci Signal. 2019 Oct 15;12(603). pii: eaaw9315. doi: 10.1126/scisignal.aaw9315. PubMed PMID: 31615901.
Allocco AA, Jin SC, Duy PQ, Furey CG, Zeng X, Dong W, Nelson-Williams C, Karimy JK, DeSpenza T, Hao LT, Reeves B, Haider S, Gunel M, Lifton RP, Kahle KT. Recessive Inheritance of Congenital Hydrocephalus With Other Structural Brain Abnormalities Caused by Compound Heterozygous Mutations in ATP1A3. Front Cell Neurosci. 2019 Sep 26;13:425. doi: 10.3389/fncel.2019.00425. eCollection 2019. PubMed PMID: 31616254; PubMed Central PMCID: PMC6775207.