HIV-1 Nef disrupts membrane-microdomain-associated anterograde transport for plasma membrane delivery of selected Src family kinases

• Verfasst von: Pan, Xiaoyu [VerfasserIn]
• Verfasst von: Geist, Miriam M. [VerfasserIn]
• Verfasst von: Rudolph, Jochen M. [VerfasserIn]
• Verfasst von: Nickel, Walter [VerfasserIn]
• Verfasst von: Fackler, Oliver Till [VerfasserIn]
• Titel: HIV-1 Nef disrupts membrane-microdomain-associated anterograde transport for plasma membrane delivery of selected Src family kinases
• Verf.angabe: Xiaoyu Pan, Miriam M. Geist, Jochen M. Rudolph, Walter Nickel and Oliver T. Fackler
• E-Jahr: 2013
• Jahr: 18 April 2013
• Umfang: 17 S.
• Fussnoten: Gesehen am 16.12.2021
• Titel Quelle: Enthalten in: Cellular microbiology
• Ort Quelle: Oxford [u.a.] : Wiley-Blackwell, 1999
• Jahr Quelle: 2013
• Band/Heft Quelle: 15(2013), 10, Seite 1605-1621
• ISSN Quelle: 1462-5822
• DOI: doi:10.1111/cmi.12148
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1782361871

Abstract

HIV-1 Nef, an essential factor in AIDS pathogenesis, boosts virus replication in vivo. As one of its activities in CD4+ T-lymphocytes, Nef potently retargets the Src family kinase (SFK) Lck but not closely related Fyn from the plasma membrane to recycling endosomes and the trans-Golgi network to tailor T-cell activation and optimize virus replication. Investigating the underlying mechanism we find Lck retargeting involves removal of the kinase from membrane microdomains. Moreover, Nef interferes with rapid vesicular transport of Lck to block anterograde transport and plasma membrane delivery of newly synthesized Lck. The sensitivity of Lck to Nef does not depend on functional domains of Lck but requires membrane insertion of the kinase. Surprisingly, the short N-terminal SH4 domain membrane anchor of Lck is necessary and sufficient to confer sensitivity to Nef-mediated anterograde transport block and microdomain extraction. In contrast, the SH4 domain of Fyn is inert to Nef-mediated manipulation. Nef thus interferes with a specialized membrane microdomain-associated pathway for plasma membrane delivery of newly synthesized Lck whose specificity is determined by the affinity of cargo for these sorting platforms. These results provide new insight into the mechanism of Nef action and the pathways used for SFK plasma membrane delivery.