Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 62, Issue 23, Pages 2739-2749Publisher
BIRKHAUSER VERLAG AG
DOI: 10.1007/s00018-005-5293-y
Keywords
cell-penetrating peptide; protein transduction; arginine-rich peptide; heparan sulfate; endocytosis; TAT; penetratin
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Funding
- Intramural NIH HHS Funding Source: Medline
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Delivery of macromolecules into living cells by arginine-rich cell penetrating peptides (AR-CPPs) is an important new avenue for the development of novel therapeutic strategies. However, to date the mechanism of this delivery remains elusive. Recent data implicate endocytosis in the internalization of AR-CPPs and their macromolecular cargo and also indicate limited delivery of macromolecules into the cell cytoplasm and nucleus. Different types of endocytosis-clathrin-dependent endocytosis, raft/caveolin-dependent endocytosis and macropinocytosis-are all implicated in the uptake of AR- CPPs and their cargo into different cells. Cationic AR-CPPs dramatically increase uptake of conjugated molecules through efficient binding to surface proteoglycans. Whether this increase in binding can assure delivery of a sufficient amount of functionally active macromolecules into the cytoplasm and nucleus or whether there is a specific mechanism by which AR-CPPs facilitate the escape of conjugated cargo from endosomes remains to be understood.
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