Kinesin KIF4 Regulates Intracellular Trafficking and Stability of the Human Immunodeficiency Virus Type 1 Gag Polyprotein

Martinez, Nathaniel W.; Xue, Xiaoxiao; Berro, Reem; Kreitzer, Geri; Resh, Marilyn D.

doi:10.1128/jvi.00819-08

Cited by 77 publications

(82 citation statements)

References 60 publications

(84 reference statements)

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“…This is not without precedence. For example, Resh and colleagues showed that Gag transits through intracellular bodies before being trafficked to the plasma membrane (Martinez et al, 2008), and the selective knockdown of cellular RNA-binding proteins blocks HIV-1 RNA transport at distinct intracellular loci (Levesque et al, 2006). This type of selectivity of a Staufen RNP was also found in Drosophila in the SpongeBody (Snee and Macdonald, 2009).…”

Section: Discussionmentioning

confidence: 90%

Novel Staufen1 ribonucleoproteins prevent formation of stress granules but favour encapsidation of HIV-1 genomic RNA

Abrahamyan

Chatel‐Chaix

Ajamian

et al. 2010

Journal of Cell Science

116

191

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SummaryHuman immunodeficiency virus type 1 (HIV-1) Gag selects for and mediates genomic RNA (vRNA) encapsidation into progeny virus particles. The host protein, Staufen1 interacts directly with Gag and is found in ribonucleoprotein (RNP) complexes containing vRNA, which provides evidence that Staufen1 plays a role in vRNA selection and encapsidation. In this work, we show that Staufen1, vRNA and Gag are found in the same RNP complex. These cellular and viral factors also colocalize in cells and constitute novel Staufen1 RNPs (SHRNPs) whose assembly is strictly dependent on HIV-1 expression. SHRNPs are distinct from stress granules and processing bodies, are preferentially formed during oxidative stress and are found to be in equilibrium with translating polysomes. Moreover, SHRNPs are stable, and the association between Staufen1 and vRNA was found to be evident in these and other types of RNPs. We demonstrate that following Staufen1 depletion, apparent supraphysiologic-sized SHRNP foci are formed in the cytoplasm and in which Gag, vRNA and the residual Staufen1 accumulate. The depletion of Staufen1 resulted in reduced Gag levels and deregulated the assembly of newly synthesized virions, which were found to contain several-fold increases in vRNA, Staufen1 and other cellular proteins. This work provides new evidence that Staufen1-containing HIV-1 RNPs preferentially form over other cellular silencing foci and are involved in assembly, localization and encapsidation of vRNA.

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Section: Discussionmentioning

confidence: 90%

Novel Staufen1 ribonucleoproteins prevent formation of stress granules but favour encapsidation of HIV-1 genomic RNA

Abrahamyan

Chatel‐Chaix

Ajamian

et al. 2010

Journal of Cell Science

116

191

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“…Unlike synaptic vesicles, dense core vesicles and UNC-6/netrin [which were shown to accumulate in the cell body and dendrites of unc-104 mutants (Asakura et al, 2010;Hall and Hedgecock, 1991;Nonet, 1999;Ou et al, 2010;Zahn et al, 2004)], TIR-1 was not detected in the AWC cell body or dendrites in unc-104 mutants. These results suggest that unc-104 may be required for the stability of TIR-1 protein, similar to the function of kinesin KIF4 in regulating intracellular trafficking and stability of HIV-1 Gag polyprotein (Martinez et al, 2008). To rule out the possibility that the odr-3 promoter is downregulated in unc-104(e1265) mutants, the expression level of odr-3p::GFP was examined in wild-type and unc-104(e1265) mutants.…”

Section: Research Articlementioning

confidence: 99%

Microtubule-based localization of a synaptic calcium-signaling complex is required for left-right neuronal asymmetry in C. elegans

et al. 2011

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SUMMARYThe axons of C. elegans left and right AWC olfactory neurons communicate at synapses through a calcium-signaling complex to regulate stochastic asymmetric cell identities called AWC ON and AWC OFF . However, it is not known how the calcium-signaling complex, which consists of UNC-43/CaMKII, TIR-1/SARM adaptor protein and NSY-1/ASK1 MAPKKK, is localized to postsynaptic sites in the AWC axons for this lateral interaction. Here, we show that microtubule-based localization of the TIR-1 signaling complex to the synapses regulates AWC asymmetry. Similar to unc-43, tir-1 and nsy-1 loss-of-function mutants, specific disruption of microtubules in AWC by nocodazole generates two AWC ON neurons. Reduced localization of UNC-43, TIR-1 and NSY-1 proteins in the AWC axons strongly correlates with the 2AWC ON phenotype in nocodazole-treated animals. We identified kinesin motor unc-104/kif1a mutants for enhancement of the 2AWC ON phenotype of a hypomorphic tir-1 mutant. Mutations in unc-104, like microtubule depolymerization, lead to a reduced level of UNC-43, TIR-1 and NSY-1 proteins in the AWC axons. In addition, dynamic transport of TIR-1 in the AWC axons is dependent on unc-104, the primary motor required for the transport of presynaptic vesicles. Furthermore, unc-104 acts non-cell autonomously in the AWC ON neuron to regulate the AWC OFF identity. Together, these results suggest a model in which UNC-104 may transport some unknown presynaptic factor(s) in the future AWC ON cell that non-cell autonomously control the trafficking of the TIR-1 signaling complex to postsynaptic regions of the AWC axons to regulate the AWC OFF identity.

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“…KIF4A has been reported to participate in a variety of cell processes, including intracellular trafficking of HIV gag and integrin-β 1 (Martinez et al, 2008;Willemsen et al, 2014), mitotic progression (Zhu and Jiang, 2005;Wandke et al, 2012), DNA damage response (Wu et al, 2008) and brain neuron development (Midorikawa et al, 2006). It has been also reported that KIF4A was upregulated in lung cancer and could serve as a prognostic biomarker and therapeutic target for lung cancer (Taniwaki et al, 2007;Zhu et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Kinesin KIF4A is associated with chemotherapeutic drug resistance by regulating intracellular trafficking of lung resistance-related protein

Pan

Zhang

Zhu

et al. 2017

J. Zhejiang Univ. Sci. B

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Multidrug resistance (MDR) is the major impediment to cancer chemotherapy. The expression of lung resistance-related protein (LRP), a non-ATP-binding cassette (ABC) transporter, is high in tumor cells, resulting in their resistance to a variety of cytotoxic drugs. However, the function of LRP in tumor drug resistance is not yet explicit. Our previous studies had shown that Kinesin KIF4A was overexpressed in cisplatin (DDP)-resistant human lung adenocarcinoma cells (A549/DDP cells) compared with A549 cells. The expression of KIF4A in A549 or A549/DDP cells significantly affects cisplatin resistance but the detailed mechanisms remain unclear. Here, we performed co-immunoprecipitation experiments to show that the tail domain of KIF4A interacted with the N-terminal of LRP. Immunofluorescence images showed that both the ability of binding to LRP and the motility of KIF4A were essential for the dispersed cytoplasm distribution of LRP. Altogether, our results shed light on a potential mechanism in that motor protein KIF4A promotes drug resistance of lung adenocarcinoma cells through transporting LRP-based vaults along microtubules towards the cell membrane. Thus KIF4A might be a cisplatin resistance-associated protein and serves as a potential target for chemotherapeutic drug resistance in lung cancer.

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Kinesin KIF4 Regulates Intracellular Trafficking and Stability of the Human Immunodeficiency Virus Type 1 Gag Polyprotein

Cited by 77 publications

References 60 publications

Novel Staufen1 ribonucleoproteins prevent formation of stress granules but favour encapsidation of HIV-1 genomic RNA

Novel Staufen1 ribonucleoproteins prevent formation of stress granules but favour encapsidation of HIV-1 genomic RNA

Microtubule-based localization of a synaptic calcium-signaling complex is required for left-right neuronal asymmetry in C. elegans

Kinesin KIF4A is associated with chemotherapeutic drug resistance by regulating intracellular trafficking of lung resistance-related protein

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