Clathrin-independent endocytosis: mechanisms and function

Sandvig, Kirsten; Pust, Sascha; Skotland, Tore; Deurs, Bo van

doi:10.1016/j.ceb.2011.03.007

Cited by 208 publications

(228 citation statements)

References 66 publications

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“…However, the proton sponge effect is debated and incontrovertible experimental evidence remains elusive. An alternative hypothesis is that polyplexes are internalized via the caveolar pathway that bypasses the endolysosomal pathway altogether [19], but the existence of a physiologically relevant caveolar pathway with a role in constitutive endocytic trafficking is equally debated [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Elucidating the role of free polycations in gene knockdown by siRNA polyplexes

et al. 2016

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Future improvements of non-viral vectors for siRNA delivery require better understanding of intracellular processing and vector interactions with target cells. Here, we have compared the siRNA delivery properties of a lipid derivative of bPEI 1.8kDa (DOPE-PEI) with branched polyethyleneimine (bPEI) with average molecular weights of 1.8kDa (bPEI 1.8kDa) and 25 kDa (bPEI 25kDa). We find mechanistic differences between the DOPE-PEI conjugate and bPEI regarding siRNA condensation and intracellular processing. bPEI 1.8kDa and bPEI 25kDa have similar properties with respect to condensation capability, but are very different regarding siRNA decondensation, cellular internalization and induction of reporter gene knockdown. Lipid conjugation of bPEI 1.8kDa improves the siRNA delivery properties, but with markedly different 2 formulation requirements and mechanisms of action compared to conventional PEIs. Interestingly, strong knockdown using bPEI 25kDa is dependent on the presence of a free vector fraction which does not increase siRNA uptake. Finally, we have investigated the effect on lysosomal pH induced by these vectors to elucidate the differences in the proton sponge effect between lipid conjugated PEI and conventional PEI: Neither DOPE-PEI nor bPEI 25kDa affected lysosomal pH as a function of time, underlining that the possible proton sponge effect is not associated with changes in lysosomal pH.

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Section: Introductionmentioning

confidence: 99%

Elucidating the role of free polycations in gene knockdown by siRNA polyplexes

et al. 2016

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“…This appears to induce a lipid-phase segregation in the membrane, which is necessary for the pinching off to take place (Liu et al, 2009;Ferguson and De Camilli, 2012). A large fraction of the clathrinindependent vesicles, however, pinch off independently of dynamin (Sandvig et al, 2011). In this case, the energy could be provided by the mechanochemical feedback predicted by a model initially developed for yeast (Liu et al, 2009).…”

Section: Fission Of the Neck And Pinching Off Of Endocytic Vesiclesmentioning

confidence: 99%

Cell surface dynamics – how Rho GTPases orchestrate the interplay between the plasma membrane and the cortical cytoskeleton

Curtis

Meldolesi

2012

Journal of Cell Science

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SummarySmall GTPases are known to regulate hundreds of cell functions. In particular, Rho family GTPases are master regulators of the cytoskeleton. By regulating actin nucleation complexes, Rho GTPases control changes in cell shape, including the extension and/or retraction of surface protrusions and invaginations. Protrusion and invagination of the plasma membrane also involves the interaction between the plasma membrane and the cortical cytoskeleton. This interplay between membranes and the cytoskeleton can lead to an increase or decrease in the plasma membrane surface area and its tension as a result of the fusion (exocytosis) or internalization (endocytosis) of membranous compartments, respectively. For a long time, the cytoskeleton and plasma membrane dynamics were investigated separately. However, studies from many laboratories have now revealed that Rho GTPases, their modulation of the cytoskeleton, and membrane traffic are closely connected during the dynamic remodeling of the cell surface. Arf-and Rab-dependent exocytosis of specific vesicles contributes to the targeting of Rho GTPases and their regulatory factors to discrete sites of the plasma membrane. Rho GTPases regulate the tethering of exocytic vesicles and modulate their subsequent fusion. They also have crucial roles in the different forms of endocytosis, where they participate in the sorting of membrane domains as well as the sculpting and sealing of membrane flasks and cups. Here, we discuss how cell surface dynamics depend on the orchestration of the cytoskeleton and the plasma membrane by Rho GTPases.

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“…The wealth of proteins that participate in raft signaling events also gives rise to a number of different CIE pathways which differ for (i) fission machinery (i.e. dynamin-dependence), (ii) coat composition and (iii) Rab effector specificity (reviewed in [4,32,50]). Both CME and CIE forms participate in Notch signaling activation and regulation.…”

Section: Types Of Endocytosis and Their Regulationmentioning

confidence: 99%

“…Regarding these mechanisms, there are multiple forms of endocytosis that act concomitantly in the cell (reviewed in [4,[31][32][33]). The best studied, and perhaps the most common, forms are clathrin-based.…”

Section: Types Of Endocytosis and Their Regulationmentioning

confidence: 99%

“…It is now many years since evidence for clathrin-independent endocytosis (CIE) has been accumulated, although the mechanism behind this process is as yet poorly characterized. The development of specialized techniques, reagents and markers to trace endocytosis has unveiled a whole new world of internalization routes that persist after inhibition of the clathrin function (reviewed in [32,[48][49][50]). A common finding is the exquisite sensitivity of CIE to cholesterol depletion, although CME is also somewhat sensitive to cholesterol levels, and some forms of CIE can still occur without membrane cholesterol [51].…”

Section: Types Of Endocytosis and Their Regulationmentioning

confidence: 99%

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