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Rab3D is critical for secretory granule maturation in PC12 cells. 2013

Tanja Kögel, and Rüdiger Rudolf, and Erlend Hodneland, and John Copier, and Romano Regazzi, and Sharon A Tooze, and Hans-Hermann Gerdes
Department of Biomedicine, University of Bergen, Bergen, Norway.

Neuropeptide- and hormone-containing secretory granules (SGs) are synthesized at the trans-Golgi network (TGN) as immature secretory granules (ISGs) and complete their maturation in the F-actin-rich cell cortex. This maturation process is characterized by acidification-dependent processing of cargo proteins, condensation of the SG matrix and removal of membrane and proteins not destined to mature secretory granules (MSGs). Here we addressed a potential role of Rab3 isoforms in these maturation steps by expressing their nucleotide-binding deficient mutants in PC12 cells. Our data show that the presence of Rab3D(N135I) decreases the restriction of maturing SGs to the F-actin-rich cell cortex, blocks the removal of the endoprotease furin from SGs and impedes the processing of the luminal SG protein secretogranin II. This strongly suggests that Rab3D is implicated in the subcellular localization and maturation of ISGs.

UI MeSH Term Description Entries
D000199 Actins Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle. F-Actin,G-Actin,Actin,Isoactin,N-Actin,alpha-Actin,alpha-Isoactin,beta-Actin,gamma-Actin,F Actin,G Actin,N Actin,alpha Actin,alpha Isoactin,beta Actin,gamma Actin
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016716 PC12 Cells A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation. Pheochromocytoma Cell Line,Cell Line, Pheochromocytoma,Cell Lines, Pheochromocytoma,PC12 Cell,Pheochromocytoma Cell Lines
D045683 Furin A proprotein convertase with specificity for the proproteins of PROALBUMIN; COMPLEMENT 3C; and VON WILLEBRAND FACTOR. It has specificity for cleavage near paired ARGININE residues that are separated by two amino acids. Dibasic Processing Enzyme,Furin Protein,Paired Basic Amino Acid Cleaving Enzyme,SPC1 Proteinase,Processing Enzyme, Dibasic
D050505 Mutant Proteins Proteins produced from GENES that have acquired MUTATIONS. Mutant Protein,Protein, Mutant,Proteins, Mutant
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D053381 Secretogranin II A type of chromogranin which was initially characterized in the ANTERIOR PITUITARY GLAND. It is found in several species including human, rat, mouse, and others. Secretogranin II is an acidic protein of 559 to 586 amino acid residues that can stimulate DOPAMINE release from neurons and release of pituitary GONADOTROPINS. Chromogranin C
D055099 Neuroendocrine Cells Specialized NEURONS that produce hormones, such as NEUROPEPTIDES or BIOGENIC AMINES. They generally are in the NERVOUS SYSTEM, such as HYPOTHALAMUS, but can be found in other organs or systems. These neurons contain dense neurosecretory granules and PROPROTEIN CONVERTASES allowing the rapidly release of NEUROHORMONES into the blood circulation upon stimulation. Endocrine Neurons,Cell, Neuroendocrine,Cells, Neuroendocrine,Endocrine Neuron,Neuroendocrine Cell,Neuron, Endocrine,Neurons, Endocrine
D020692 rab3 GTP-Binding Proteins A genetically related subfamily of RAB GTP-BINDING PROTEINS involved in calcium-dependent EXOCYTOSIS. This enzyme was formerly listed as EC 3.6.1.47. rab3 Protein,rab3 Proteins,GTP-Binding Proteins, rab3,rab3 GTP Binding Proteins
D022142 Secretory Vesicles Vesicles derived from the GOLGI APPARATUS containing material to be released at the cell surface. SLMVs,Secretory Granules,Synaptic Like Microvesicles,Synaptic-Like Microvesicles,Zymogen Granules,Condensing Vacuoles,Condensing Vacuole,Granule, Secretory,Granule, Zymogen,Microvesicle, Synaptic-Like,Secretory Granule,Secretory Vesicle,Synaptic Like Microvesicle,Synaptic-Like Microvesicle,Vacuole, Condensing,Vesicle, Secretory,Zymogen Granule

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