Piccolo, a Presynaptic Zinc Finger Protein Structurally Related to Bassoon

Fenster, Steven D.; Chung, Wook Joon; Zhai, R. Grace; Cases-Langhoff, C; Voss, Britta; Garner, Abigail M.; Kaempf, Udo; Kindler, Stefan; Gundelfinger, Eckart D.; Garner, Craig C.

doi:10.1016/s0896-6273(00)80883-1

Cited by 267 publications

(269 citation statements)

References 46 publications

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“…PRA1 is a protein that is localized primarily to the Golgi complex (14) and post-Golgi compartments (15). We have shown here that point mutations of PRA1 can alter its cellular localization as well as vesicle trafficking.…”

Section: Discussionmentioning

confidence: 74%

Disruption of Golgi Morphology and Trafficking in Cells Expressing Mutant Prenylated Rab Acceptor-1

Gougeon¹,

Prosser²,

DaSilva

et al. 2002

Journal of Biological Chemistry

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Prenylated Rab acceptor (PRA1) is a protein that binds Rab GTPases and the v-SNARE VAMP2. The protein is localized to the Golgi complex and post-Golgi vesicles. To determine its functional role, we generated a number of point mutations and divided them into three classes based on cellular localization. Class A mutants were retained in the endoplasmic reticulum (ER) and exerted an inhibitory effect on transport of vesicular stomatitis virus envelope glycoprotein (VSVG) from the ER to Golgi as well as to the plasma membrane. Class B mutants exhibited a highly condensed Golgi complex and inhibited exit of anterograde cargo from this organelle. Class C mutants exhibited an intermediate phenotype with Golgi and ER localization along with extensive tubular structures emanating from the Golgi complex. There was a direct correlation between the cellular phenotype and binding to Rab and VAMP2. Class A and C mutants showed a significant decrease in Rab and VAMP2 binding, whereas an increase in binding was observed in the class B mutants. Thus, PRA1 is required for vesicle formation from the Golgi complex and might be involved in recruitment of Rab effectors and SNARE proteins during cargo sequestration.Rab GTPases constitute the largest group within the Ras superfamily. They regulate vesicle trafficking by cycling through active membrane-bound GTP-and inactive cytosolic GDP-bound states. Membrane localization requires modification of the cysteine-containing motif at the carboxyl terminus by prenyl residues. Cycling between the membrane and cytosol is mediated by GDP dissociation inhibitor (GDI), 1 which extracts GDP-bound Rab from the membrane. Activation through guanine nucleotide exchange at the membrane is catalyzed by a guanine nucleotide exchange factor, of which a number have been identified in mammals (1, 2).Vesicular transport through the secretory pathway undergoes a number of discrete steps each involving budding, membrane remodeling, targeting, docking, and fusion. In ER to Golgi transport, anterograde cargo proteins such as VSVG are selectively transported to the Golgi along with resident ER proteins with the latter retrieved by a salvage process that recognizes distinct motifs within the protein (3). These transport vesicles contain an electron-dense coat assembled under the control of the small GTPase ARF (4). The fungal metabolite brefeldin A (BFA) inhibits ARF activation by stabilizing the inactive ARF-guanine nucleotide exchange factor (GEF) complex (5) resulting in retrograde transport of Golgi content to the ER. At the Golgi complex, cargo proteins destined for postGolgi locations are sorted into distinct carriers upon exit from the trans face, whereas Golgi resident proteins such as mannosidase II (Man II) are selectively retrieved in COPI-coated vesicles and returned to the cis face (6).Vesicle fusion is mediated by the core SNARE complex consisting of the vesicle protein VAMP, or synaptobrevin, and two other membrane proteins, syntaxin and SNAP-25 (7). Rab effectors play a regulatory role in this pro...

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Section: Discussionmentioning

confidence: 74%

Disruption of Golgi Morphology and Trafficking in Cells Expressing Mutant Prenylated Rab Acceptor-1

Gougeon¹,

Prosser²,

DaSilva

et al. 2002

Journal of Biological Chemistry

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“…Briefly, proteins processed from membrane fractions, cytosolic fractions and total cell lysates were analyzed by Far Westerns using protocols described (Fenster et al, 2000). Membranes were probed with 300-500 nM His-Cltx followed by detection of the bound proteins using an anti-His mAb (Clonetech, 1:5000).…”

Section: Overlay Assays (Far Westerns)mentioning

confidence: 99%

A role for ion channels in glioma cell invasion

McFerrin¹,

2005

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Many cells, including neuronal and glial progenitor cells, stem cells and microglial cells, have the capacity to move through the extracellular spaces of the developing and mature brain. This is particularly pronounced in astrocyte-derived tumors, gliomas, which diffusely infiltrate the normal brain. Although a significant body of literature exists regarding signals that are involved in the guidance of cells and their processes, little attention has been paid to cell-shape and cell-volume changes of migratory cells. However, extracellular spaces in the brain are very narrow and represent a major obstacle that requires cells to dynamically regulate their volume. Recent studies in glioma cells show that this involves the secretion of Cl − and K + with water. Pharmacological inhibition of Cl − channels impairs their ability to migrate and limits tumor progression in experimental tumor models. One Cl − -channel inhibitor, chlorotoxin, is currently in Phase II clinical trials to treat malignant glioma. This article reviews our current knowledge of cell-volume changes and the role of ion channels during the migration of glioma cells. It also discusses evidence that supports the importance of channel-mediated cell-volume changes in the migration of immature neurons and progenitor cells during development. New unpublished data is presented, which demonstrates that Cl − and K + channels involved in cell shrinkage localize to lipid-raft domains on the invadipodia of glioma cells and that their presence might be regulated by trafficking of these proteins in and out of lipid rafts.

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“…In human, yeast, and mouse, PRA1 resides predominantly in the Golgi apparatus (Liang and Li, 2000;Huh et al, 2003;Sivars et al, 2003). However, PRA1 proteins have been reported in different trafficking compartments, such as the ER (Abdul-Ghani et al, 2001;Schweneker et al, 2005;Liu et al, 2006), synaptic vesicles (Fenster et al, 2000), COPI and COPII vesicles (Otte et al, 2001;Gilchrist et al, 2006), and endosomes (Schweneker et al, 2005;Geerts et al, 2007). To determine the subcellular localization of the 19 AtPRA1 proteins, their full-length open reading frames were fused to the enhanced GFP reporter protein (EGFP) and stably produced in Arabidopsis seedlings.…”

Section: Subcellular Localization Of the Atpra1 Proteins In Arabidopsismentioning

confidence: 99%

“…PRA1s are small transmembrane proteins omnipresent in different vesicle trafficking events and interact with various kinds of proteins. In chemical synapses, PRA1 associates with Piccolo, a zinc finger protein of the presynaptic cytoskeletal matrix, suggesting a function in synaptic vesicle trafficking (Fenster et al, 2000). PRA1 also interacts with other prenylated small GTPases, such as the mouse Ha-Ras, N-Ras, TC21, and RhoA, as well as with the v-SNARE protein VAMP2 (Martincic et al, 1997;Figueroa et al, 2001), and it plays a role as modulator of the neural Glu transporter excitatory amino acid carrier 1 (Akiduki et al, 2007).…”

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confidence: 99%

ThePRA1Gene Family in Arabidopsis

Kamei

Boruc²,

Vandepoele³

et al. 2008

Plant Physiology

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Prenylated Rab acceptor 1 (PRA1) domain proteins are small transmembrane proteins that regulate vesicle trafficking as receptors of Rab GTPases and the vacuolar soluble N-ethylmaleimide-sensitive factor attachment receptor protein VAMP2. However, little is known about PRA1 family members in plants. Sequence analysis revealed that higher plants, compared with animals and primitive plants, possess an expanded family of PRA1 domain-containing proteins. The Arabidopsis (Arabidopsis thaliana) PRA1 (AtPRA1) proteins were found to homodimerize and heterodimerize in a manner corresponding to their phylogenetic distribution. Different AtPRA1 family members displayed distinct expression patterns, with a preference for vascular cells and expanding or developing tissues. AtPRA1 genes were significantly coexpressed with Rab GTPases and genes encoding vesicle transport proteins, suggesting an involvement in the vesicle trafficking process similar to that of their animal counterparts. Correspondingly, AtPRA1 proteins were localized in the endoplasmic reticulum, Golgi apparatus, and endosomes/ prevacuolar compartments, hinting at a function in both secretory and endocytic intracellular trafficking pathways. Taken together, our data reveal a high functional diversity of AtPRA1 proteins, probably dealing with the various demands of the complex trafficking system.

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Piccolo, a Presynaptic Zinc Finger Protein Structurally Related to Bassoon

Cited by 267 publications

References 46 publications

Disruption of Golgi Morphology and Trafficking in Cells Expressing Mutant Prenylated Rab Acceptor-1

Disruption of Golgi Morphology and Trafficking in Cells Expressing Mutant Prenylated Rab Acceptor-1

A role for ion channels in glioma cell invasion

ThePRA1Gene Family in Arabidopsis

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