Protein Kinase D2 Assembles a Multiprotein Complex at the Trans-Golgi Network to Regulate Matrix Metalloproteinase Secretion.
Vesicle formation and fission are tightly regulated at the trans-Golgi network (TGN) during constitutive secretion. Two major protein families regulate these processes: members of the adenosyl-ribosylation factor family of small G-proteins (ARFs) and the protein kinase D (PKD) family of serine/threonine kinases. The functional relationship between these two key regulators of protein transport from the TGN so far is elusive. We here demonstrate the assembly of a novel functional protein complex at the TGN and its key members: cytosolic PKD2 binds ARF-like GTPase (ARL1) and shuttles ARL1 to the TGN. ARL1, in turn, localizes Arfaptin2 to the TGN. At the TGN, where PKD2 interacts with active ARF1, PKD2, and ARL1 are required for the assembly of a complex comprising of ARF1 and Arfaptin2 leading to secretion of matrix metalloproteinase-2 and -7. In conclusion, our data indicate that PKD2 is a core factor in the formation of this multiprotein complex at the TGN that controls constitutive secretion of matrix metalloproteinase cargo.
From the Department of Internal Medicine I, Ulm University, Albert Einstein Allee 23, D-89081 Ulm, Germany and tim.eiseler@uniklinik-ulm.de.
Tim
T
Eiseler
From the Department of Internal Medicine I, Ulm University, Albert Einstein Allee 23, D-89081 Ulm, Germany and.
Christoph
C
Wille
the Department of Internal Medicine I, Martin-Luther University Halle-Wittenberg, Ernst-Grube, Strasse 40, D-06120 Halle (Saale), Germany.
Conny
C
Koehler
From the Department of Internal Medicine I, Ulm University, Albert Einstein Allee 23, D-89081 Ulm, Germany and.
Anett
A
Illing
From the Department of Internal Medicine I, Ulm University, Albert Einstein Allee 23, D-89081 Ulm, Germany and thomas.seufferlein@uniklinik-ulm.de.
Thomas
T
Seufferlein
D020823:ADP-Ribosylation Factor 1 / Q000378:metabolism; D020727:ADP-Ribosylation Factors / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism*; D011485:Protein Binding; D000091283:Protein Kinase D2; D011494:Protein Kinases / Q000378:metabolism*; D021381:Protein Transport; D021601:trans-Golgi Network / Q000378:metabolism*
C101158:ARFIP2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D007527:Isoenzymes; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D000091283:Protein Kinase D2; D006160:Guanosine Triphosphate; D011494:Protein Kinases; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2; C097313:ADP-ribosylation factor related proteins; D020823:ADP-Ribosylation Factor 1; D020727:ADP-Ribosylation Factors
ADP ribosylation factor (ARF); metalloprotease; protein kinase D (PKD); secretion; vesicles