Biomaterial Database

Secretory cargo sorting by Ca2+-dependent Cab45 oligomerization at the trans-Golgi network. 2016

Alvaro H Crevenna, and Birgit Blank, and Andreas Maiser, and Derya Emin, and Jens Prescher, and Gisela Beck, and Christine Kienzle, and Kira Bartnik, and Bianca Habermann, and Mehrshad Pakdel, and Heinrich Leonhardt, and Don C Lamb, and Julia von Blume

Physical Chemistry, Department of Chemistry Center for Nanoscience, Nanosystems Initiative Munich and Center for Integrated Protein Science Munich, Ludwig Maximilians University Munich, 81377 Munich, Germany vonblume@biochem.mpg.de alvaro.crevenna@cup.uni-muenchen.de.

Sorting and export of transmembrane cargoes and lysosomal hydrolases at the trans-Golgi network (TGN) are well understood. However, elucidation of the mechanism by which secretory cargoes are segregated for their release into the extracellular space remains a challenge. We have previously demonstrated that, in a reaction that requires Ca(2+), the soluble TGN-resident protein Cab45 is necessary for the sorting of secretory cargoes at the TGN. Here, we report that Cab45 reversibly assembles into oligomers in the presence of Ca(2+) These Cab45 oligomers specifically bind secretory proteins, such as COMP and LyzC, in a Ca(2+)-dependent manner in vitro. In intact cells, mutation of the Ca(2+)-binding sites in Cab45 impairs oligomerization, as well as COMP and LyzC sorting. Superresolution microscopy revealed that Cab45 colocalizes with secretory proteins and the TGN Ca(2+) pump (SPCA1) in specific TGN microdomains. These findings reveal that Ca(2+)-dependent changes in Cab45 mediate sorting of specific cargo molecules at the TGN.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D011506	Proteins	Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.	Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002135	Calcium-Binding Proteins	Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.	Calcium Binding Protein,Calcium-Binding Protein,Calcium Binding Proteins,Binding Protein, Calcium,Binding Proteins, Calcium,Protein, Calcium Binding,Protein, Calcium-Binding
D006023	Glycoproteins	Conjugated protein-carbohydrate compounds including MUCINS; mucoid, and AMYLOID glycoproteins.	C-Glycosylated Proteins,Glycosylated Protein,Glycosylated Proteins,N-Glycosylated Proteins,O-Glycosylated Proteins,Glycoprotein,Neoglycoproteins,Protein, Glycosylated,Proteins, C-Glycosylated,Proteins, Glycosylated,Proteins, N-Glycosylated,Proteins, O-Glycosylated
D006367	HeLa Cells	The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays.	Cell, HeLa,Cells, HeLa,HeLa Cell
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001692	Biological Transport	The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.	Transport, Biological,Biologic Transport,Transport, Biologic
D055571	Secretory Pathway	A series of sequential intracellular steps involved in the transport of proteins (such as hormones and enzymes) from the site of synthesis to outside the cell. The pathway involves membrane-bound compartments through which the newly synthesized proteins undergo POST-TRANSLATIONAL MODIFICATIONS, packaging, storage, or transportation to the PLASMA MEMBRANE for secretion.	Secretion Pathway,Secretion Process,Secretory Process,Secretion Pathways,Secretion Processes,Secretory Pathways,Secretory Processes
D020013	Calcium Signaling	Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.	Calcium Oscillations,Calcium Waves,Calcium Puffs,Calcium Sparks,Calcium Spikes,Calcium Oscillation,Calcium Puff,Calcium Signalings,Calcium Spark,Calcium Spike,Calcium Wave,Oscillation, Calcium,Oscillations, Calcium,Puff, Calcium,Puffs, Calcium,Signaling, Calcium,Signalings, Calcium,Spark, Calcium,Sparks, Calcium,Spike, Calcium,Spikes, Calcium,Wave, Calcium,Waves, Calcium