Cellular Uptake of Unconjugated TAT Peptide Involves Clathrin-dependent Endocytosis and Heparan Sulfate Receptors*
By Jean-Philippe Richard, K. Melikov, H. Brooks, P. Prévot, B. Lebleu, L. Chernomordik. Journal of Biological Chemistry, 2005
611 citations recorded by the source corpus.
Delivery of macromolecules mediated by protein transduction domains (PTDs) attracts a lot of interest due to its therapeutic and biotechnological potential. A major reevaluation of the mechanism of PTD-mediated internalization and the role of endocytosis in this mechanism has been recently initiated. Here, we demonstrate that the entry of TAT peptide (one of the most widely used PTDs) into different primary cells is ATPand temperature-dependent, indicating the involvement of endocytosis. Specific inhibitors of clathrin-dependent endocytosis partially inhibit TAT peptide uptake, implicating this pathway in TAT peptide entry. In contrast, the caveolin-dependent pathway is not essential for the uptake of unconjugated TAT peptide as evidenced by the efficient internalization of TAT in the presence of the known inhibitors of raft/caveolin-dependent pathway and for cells lacking or deficient in caveolin-1 expression. Whereas a significant part of TAT peptide uptake involves heparan sulfate receptors, efficient internalization of peptide is observed even in their absence, indicating the involvement of other receptors. Our results suggest that unconjugated peptide might follow endocytic pathways different from those utilized by TAT peptide conjugated to different proteins.
Subfields: Immunology and Allergy, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/be695d87da42274b14d6b9e38a40a5abf85b1690
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Molecular Biology
Citations in the corpus
- Uptake Pathways and Subsequent Intracellular Trafficking in Nonviral Gene Delivery (2006, background): “…charged cell surface constituents, such as heparan sulfate proteoglycans and integrins play a role in the cellular binding of positively charged lipoplexes, polyplexes , or even cationic peptides, such as TAT (Behr et al., 1989; Labat-Moleur et al., 1996; Tyagi et al., 2001; Richard et al., 2005).”
- Cell‐penetrating peptides: 20 years later, where do we stand? (2013, background): “internalization of Tat peptide [140], and caveolin knock-out was shown not to affect the uptake of Tat peptide in baby hamster kid-”
- Twenty years of cell-penetrating peptides: from molecular mechanisms to therapeutics (2009, neutral): “…of cationic CPPs (Wadia et al., 2004; Kaplan et al., 2005), other endocytotic pathways including clathrin- and caveolin-dependent endocytosis (Richard et al., 2005; Ziegler et al., 2005) and transGolgi network-mediated internalization (Fischer et al., 2005) have been described for CPPs.”
- Cell-penetrating peptides: design, synthesis, and applications. (2014, background): “indicating the involvement of a clathrin-dependent pathway.(133) In addition, studies on the uptake of these peptides in HeLa cells confirmed that the presence of caveolae is not required for cellular internalization.”