Secretion without Golgi.
A growing number of proteins devoid of signal peptides have been demonstrated to be released through the non-classical pathways independent of endoplasmic reticulum and Golgi. Among them are two potent proangiogenic cytokines FGF1 and IL1alpha. Stress-induced transmembrane translocation of these proteins requires the assembly of copper-dependent multiprotein release complexes. It involves the interaction of exported proteins with the acidic phospholipids of the inner leaflet of the cell membrane and membrane destabilization. Not only stress, but also thrombin treatment and inhibition of Notch signaling stimulate the export of FGF1. Non-classical release of FGF1 and IL1alpha presents a promising target for treatment of cardiovascular, oncologic, and inflammatory disorders.
Prudovsky
Igor
I
Maine Medical Center Research Institute, Maine Medical Center, Scarborough, Maine 04074, USA. prudoi@mmc.org
Tarantini
Francesca
F
Landriscina
Matteo
M
Neivandt
David
D
Soldi
Raffaella
R
Kirov
Aleksandr
A
Small
Deena
D
Kathir
Karuppanan Muthusamy
KM
Rajalingam
Dakshinamurthy
D
Kumar
Thallapuranam Krishnaswamy Suresh
TK
D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D053582:Interleukin-1alpha / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism; D021381:Protein Transport; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction