Identification of a signal peptide for unconventional secretion.
Homeoproteins are a class of transcription factors defined by the structure of their DNA-binding domain, the homeodomain. In addition to their nuclear cell-autonomous activities, homeoproteins transfer between cells, thanks to two separate steps of secretion and internalization, which both rely on unconventional mechanisms. Internalization is driven by the third helix of the homeodomain (Penetratin) through a non-vesicular and endocytosis-independent mechanism. In contrast, homeoprotein secretion involves vesicular compartments and requires the presence of a sequence of 11 amino acids (Sec sequence) spanning between the second and third helix of the homeodomain. In this study, we report that the SecPen polypeptide, which combines the two identified domains, Penetratin and Sec, bears all of the necessary information to go in and out of cells. We have analyzed key mechanisms and demonstrated that this peptide can efficiently cross a tight junction epithelium.
Dupont
Edmond
E
Homeoprotein Cell Biology Group, CNRS UMR 8542, Ecole Normale Supérieure, 75230 Paris Cedex 05, France.
Prochiantz
Alain
A
Joliot
Alain
A
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D019921:Biotinylation; D002352:Carrier Proteins / Q000737:chemistry* / Q000502:physiology; D002460:Cell Line; D057846:Cell-Penetrating Peptides; D004247:DNA / Q000737:chemistry; D004285:Dogs; D006056:Golgi Apparatus / Q000378:metabolism; D018398:Homeodomain Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary
D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D018398:Homeodomain Proteins; D010455:Peptides; D021382:Protein Sorting Signals; D004247:DNA; C414409:penetratin