title: Cellular uptake of the Antennapedia homeodomain polypeptide by macropinocytosis.
abstract: Antennapedia homeodomain has been shown to be able to translocate from extracellular space into the cytoplasm of cells in a receptor-independent manner. Its third α-helix domain, designated as "Penetratin", was proposed to be the functional transduction domain that is responsible for the translocation, and it is widely used for intracellular delivery of various exogenous proteins. Although Penetratin has been regarded to be the only element conferring the capacity on its parent polypeptide to penetrate through the plasma membrane, we found that the complete Antennapedia homeodomain exhibits an appreciably higher level of translocation efficiency as compared to Penetratin. Pharmacological analysis demonstrated that macropinocytic endocytosis plays a significant role underlying the process of the homeodomain internalization, and this is consistent with the observation that internalized polypeptide co-localizes with a fluid phase dye. Our results identify macropinocytosis as a major mechanism by which Antennapedia homeodomain obtains the access to the interior of cells, providing a novel perspective in the field of protein translocation and transduction.
authors.affiliation: Biozentrum der Universität Basel, Growth and Development, CH-4056 Basel, Switzerland.
authors.forename: Xiaomo
authors.initials: X
authors.lastname: Wu
authors.affiliation: Biozentrum der Universität Basel, Growth and Development, CH-4056 Basel, Switzerland. Electronic address: Walter.Gehring@unibas.ch.
authors.forename: Walter
authors.initials: W
authors.lastname: Gehring
mesh_terms: D000595:Amino Acid Sequence; D051943:Antennapedia Homeodomain Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010873:Pinocytosis; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D051943:Antennapedia Homeodomain Protein; D018398:Homeodomain Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C497138:penetratin (43-58), human
keywords: Antennapedia homeodomain; Cell-Penetrating Peptides (CPPs); Penetratin