Exploitation of Microtubule Cytoskeleton and Dynein during Parvoviral Traffic toward the Nucleus

Suikkanen, Sanna; Aaltonen, Tuula M.; Nevalainen, Marjukka; Välilehto, Outi; Lindholm, Laura; Vuento, Matti; Vihinen‐Ranta, Maija

doi:10.1128/jvi.77.19.10270-10279.2003

Cited by 95 publications

(89 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[22][23][24][25][26] In these studies, significant accumulation of viral particles near the nucleus was seen within 1-2 h. The actin network can also act as a transport conduit, as demonstrated by bacculovirus, which uses the actin network exclusively for transport, 27 and HIV, which uses both actin and microtubule networks for cytoplasmic trafficking. 22 Nonviral vectors, depending on their mode of transfection, can also use cytoskeletal machinery to travel toward the nucleus.…”

Section: The Percent Of Apoptotic Cells (7sd) Is Shownmentioning

confidence: 79%

Cyclic stretch-induced reorganization of the cytoskeleton and its role in enhanced gene transfer

et al. 2006

View full text Add to dashboard Cite

Cyclic stretch is known to alter a number of cellular and subcellular processes, including those involved in nonviral gene delivery. We have previously shown that moderate equibiaxial cyclic stretch (10% change in basement membrane area, 0.5 Hz, 50% duty cycle) of human pulmonary A549 cells enhances gene transfer and expression of reporter plasmid DNA in vitro, and that this phenomena may be due to alterations in cytoplasmic trafficking. Although the path by which plasmid DNA travels through the cytoplasm toward the nucleus is not well understood, the cytoskeleton and the constituents of the cytoplasm are known to significantly hinder macromolecular diffusion. Using biochemical techniques and immunofluorescence microscopy, we show that both the microfilament and microtubule networks are significantly reorganized by equibiaxial cyclic stretch. Prevention of this reorganization through the use of cytoskeletal stabilizing compounds mitigates the stretchinduced increase in gene expression, however, depolymerization in the absence of stretch is not sufficient to increase gene expression. These results suggest that cytoskeletal reorganization plays an important role in stretch-induced gene transfer and expression. Gene Therapy (2006) 13, 725-731.

show abstract

Section: The Percent Of Apoptotic Cells (7sd) Is Shownmentioning

confidence: 79%

Cyclic stretch-induced reorganization of the cytoskeleton and its role in enhanced gene transfer

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Many animal viruses rely on microtubule-based transport for delivery to the nuclear envelope, where the viral genome is released through the nuclear pores (29,30). Salman et al (23) demonstrated integration of the microtubule delivery and nucleocytoplasmic transport systems in an animal cell model, showing that the same NLS responsible for translocation through nuclear pores also invoked active, dyneinmediated transport along microtubules.…”

Section: Discussionmentioning

confidence: 99%

Effect of protein kinase A on accumulation of brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1) in HepG2 cell nuclei

Citterio

Jones

Pacheco–Rodriguez

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Brefeldin A-inhibited guanine nucleotide-exchange proteins, BIG1 and BIG2, are activators of ADP-ribosylation factor GTPases that are essential for regulating vesicular traffic among intracellular organelles. Biochemical analyses and immunofluorescence microscopy demonstrated BIG1 in nuclei as well as membranes and cytosol of serum-starved HepG2 cells. Within 20 min after addition of 8-Br-cAMP, BIG1 accumulated in nuclei, and this effect was blocked by protein kinase A (PKA) inhibitors H-89 and PKI, suggesting a dependence on PKA-catalyzed phosphorylation. BIG2 localization was not altered by cAMP, nor did BIG2 small interfering RNA influence nuclear accumulation of BIG1 induced by cAMP. Mutant BIG1 (S883A) in which Ala replaced Ser-883, a putative PKA phosphorylation site, did not move to the nucleus with cAMP addition, whereas replacement with Asp (S883D) resulted in nuclear accumulation of BIG1 without or with cAMP exposure, consistent with the mechanistic importance of a negative charge at that site. Mutation (712KPK714) of the nuclear localization signal inhibited BIG1 accumulation in nuclei, and PKA-catalyzed phosphorylation of S883, although necessary, was not sufficient for nuclear accumulation, as shown by the double mutation S883D͞ nuclear localization signal. A role for microtubules in cAMP-induced translocation of BIG1 is inferred from its inhibition by nocodazole. Thus, two more critical elements of BIG1 molecular structure were identified, as well as the potential function of microtubules in a novel PKA effect on BIG1 translocation.ADP-ribosylation factor ͉ protein trafficking ͉ A kinase-anchoring protein M ammalian ADP-ribosylation factors (ARFs) comprise six 20-kDa GTP-binding proteins with essential regulatory roles in the formation of membrane trafficking vesicles. These vesicles bud from a donor membrane and fuse with a target membrane to deliver cargo molecules (1-3). Conversion of ARF from a cytosolic GDP-bound inactive state to a GTP-bound active form that is tightly membrane-associated is accelerated by guanine nucleotide-exchange factors (GEFs) (4). All known ARF GEFs contain a Sec7 domain of Ϸ200 aa that catalyzes ARF activation (5-7). The large-molecular-weight BIG1, BIG2, and GBF1, which localize in Golgi regions, are, with different sensitivities, inhibited by the fungal fatty acid metabolite brefeldin A (8-10). The Ϸ200-kDa BIG1 and Ϸ190-kDa BIG2 were first purified together from bovine brain cytosol on the basis of their BFA-inhibited GEF activities (11) and appeared to exist as parts of the same macromolecular complex(es) in HepG2 cells (12). When these cells were growing in medium with serum, BIG1 was primarily cytosolic and Golgi-associated. After overnight incubation without serum, a large fraction of endogenous BIG1 was found in the nuclei localized with nucleoporin p62 at the nuclear envelope (probably in transit between nucleus and cytoplasm), as well as in the nuclear matrix and nucleoli (13).The cAMP-dependent protein kinase A (PKA) is a tetrameric protein comprising two ca...

show abstract

“…170 Numerous viruses have taken advantage of this intracellular transport system and utilize dynein-mediated trafficking to catch a ride to nuclear periphery. [171][172][173][174][175][176] While in some cases intact cytoskeletal elements are Intracellular trafficking of nonviral vectors LK Medina-Kauwe et al required for appropriate nonviral vector trafficking in cells, in other cases, the cytoskeleton may either interfere with intracellular translocation or direct nonviral vectors to undesirable sites within the cell. In many of the studies mentioned earlier, the contribution of the cytoskeleton to vector uptake and vesicle trafficking was described.…”

Section: Cytoskeletal Factorsmentioning

confidence: 99%

Intracellular trafficking of nonviral vectors

2005

View full text Add to dashboard Cite

Exploitation of Microtubule Cytoskeleton and Dynein during Parvoviral Traffic toward the Nucleus

Cited by 95 publications

References 64 publications

Cyclic stretch-induced reorganization of the cytoskeleton and its role in enhanced gene transfer

Cyclic stretch-induced reorganization of the cytoskeleton and its role in enhanced gene transfer

Effect of protein kinase A on accumulation of brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1) in HepG2 cell nuclei

Intracellular trafficking of nonviral vectors

Contact Info

Product

Resources

About