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Rac1 and Scribble a...
Rac1 and Scribble are targets for the arrest of neurite outgrowth by TBE virus NS5
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- Wigerius, Michael (författare)
- Södertörns högskola,Stockholms universitet,Institutionen för biokemi och biofysik,Kemi,Molekylärbiologi
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- Melik, Wessam (författare)
- Södertörns högskola,Stockholms universitet,Institutionen för genetik, mikrobiologi och toxikologi,Kemi,Molekylärbiologi
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- Elväng, Annelie (författare)
- Södertörns högskola,Molekylärbiologi,Södertörns högskola, Institutionen för livsvetenskaper
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- Johansson, Magnus (författare)
- Södertörns högskola,Kemi,Internationell hälsa,Södertörns högskola, Institutionen för livsvetenskaper
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(creator_code:org_t)
- Elsevier BV, 2010
- 2010
- Engelska.
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Ingår i: Molecular and Cellular Neuroscience. - : Elsevier BV. - 1044-7431 .- 1095-9327. ; 44:3, s. 260-271
- Relaterad länk:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Tick-borne encephalitis virus (TBEV) causes extensive CNS disease in humans known as TBE, however, relatively little is known of the molecular mechanisms for its progress. Here, we now show that TBEV produces defects in neuronal development of PC12 cells through a function of the viral NS5 protein. The methyltransferase domain of NS5 is critical and sufficient for restriction of nerve growth factor induced neurite outgrowth. This effect is reversed by expression of NS5 mutants unable to bind Scribble and unexpectedly, in Scribble depleted cells with binding-competent NS5. Furthermore, we also demonstrate that the Rho GTPase Rac1 and the guanine nucleotide-exchange factor, βPIX are outcompeted by NS5 for binding to Scribble, linking to effects on neurite outgrowth by TBEV. Together, these findings provide the first experimental evidence that Rac1 and βPIX are indirect targets of NS5 acting through the multifunctional polarity protein Scribble to oppose neuronal differentiation. In conclusion, our results offer a potential mechanism by which TBEV alters neuronal circuitry and opens new avenues for therapeutic interventions.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Nyckelord
- TBEV
- NS5
- MTase
- Scribble
- Neurite morphogenesis
- Molecular mechanism of neurotropic
- Virus pathogenesis
- molekylärgenetik
- Molecular Genetics
- Biochemistry
- biokemi
- Medicine
- MEDICINE
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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