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EFA6 regulates selective polarised transport and axon regeneration from the axon initial segment
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SYSNO ASEP 0487517 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název EFA6 regulates selective polarised transport and axon regeneration from the axon initial segment Tvůrce(i) Eva, R. (GB)
Koseki, H. (GB)
Kanamarlapudi, V. (GB)
Fawcett, James (UEM-P) ORCIDZdroj.dok. Journal of Cell Science. - : Company of Biologists - ISSN 0021-9533
Roč. 130, č. 21 (2017), s. 3663-3675Poč.str. 13 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova axon regeneration ; axon transport ; neuronal polarisation Vědní obor RIV FH - Neurologie, neurochirurgie, neurovědy Obor OECD Neurosciences (including psychophysiology Institucionální podpora UEM-P - RVO:68378041 UT WOS 000414149400009 EID SCOPUS 85032824407 DOI 10.1242/jcs.207423 Anotace Central nervous system (CNS) axons lose their intrinsic ability to regenerate upon maturity, whereas peripheral nervous system (PNS) axons do not. A key difference between these neuronal types is their ability to transport integrins into axons. Integrins can mediate PNS regeneration, but are excluded from adult CNS axons along with their Rab11 carriers. We reasoned that exclusion of the contents of Rab11 vesicles including integrins might contribute to the intrinsic inability of CNS neurons to regenerate, and investigated this by performing laser axotomy. We identify a novel regulator of selective axon transport and regeneration, the ARF6 guanine-nucleotide-exchange factor (GEF) EFA6 (also known as PSD). EFA6 exerts its effects from a location within the axon initial segment (AIS). EFA6 does not localise at the AIS in dorsal root ganglion (DRG) axons, and in these neurons, ARF6 activation is counteracted by an ARF GTPase-activating protein (GAP), which is absent from the CNS, ACAP1. Depleting EFA6 from cortical neurons permits endosomal integrin transport and enhances regeneration, whereas overexpressing EFA6 prevents DRG regeneration. Our results demonstrate that ARF6 is an intrinsic regulator of regenerative capacity, implicating EFA6 as a focal molecule linking the AIS, signalling and transport.
Pracoviště Ústav experimentální medicíny Kontakt Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Rok sběru 2018
Počet záznamů: 1