Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.
The biogenesis of exosomes, small secreted vesicles involved in signalling processes, remains incompletely understood. Here, we report evidence that the syndecan heparan sulphate proteoglycans and their cytoplasmic adaptor syntenin control the formation of exosomes. Syntenin interacts directly with ALIX through LYPX(n)L motifs, similarly to retroviral proteins, and supports the intraluminal budding of endosomal membranes. Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs, and impact on the trafficking and confinement of FGF signals. This study identifies a key role for syndecan-syntenin-ALIX in membrane transport and signalling processes.
Laboratory for Glycobiology and Developmental Genetics, Department of Human Genetics, KULeuven, Campus Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium.
Maria Francesca
MF
Baietti
Zhe
Z
Zhang
Eva
E
Mortier
Aurélie
A
Melchior
Gisèle
G
Degeest
Annelies
A
Geeraerts
Ylva
Y
Ivarsson
Fabienne
F
Depoortere
Christien
C
Coomans
Elke
E
Vermeiren
Pascale
P
Zimmermann
Guido
G
David
D000818:Animals; D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D051379:Mice; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D034622:RNA Interference; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D053667:Syndecans / Q000235:genetics / Q000378:metabolism*; D053676:Syntenins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D005346:Fibroblast Growth Factors; D006497:Heparan Sulfate; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; D053667:Syndecans; D053676:Syntenins; C117020:PDCD6IP protein, human; C492144:Pdcd6ip protein, mouse