Biogenesis of Regulated Exocytotic Carriers in Neuroendocrine Cells

Eaton, Benjamin A.; Haugwitz, Michael; Lau, Dana; Moore, Helen

doi:10.1523/jneurosci.20-19-07334.2000

Cited by 111 publications

(119 citation statements)

References 29 publications

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“…In brief, two oligonucleotides (sense, 5Ј-TCATCACCGTCA-GCCTTAGTTCAAGAGACTAAGGCTGACGGTGATGATTTTTT-3Ј and ; yellow in C, F, and L, respectively), especially at the tips of the cellular processes, consistent with the results of our previous subcellular fractionation study (40). Because the Syt IV protein in undifferentiated PC12 cells is mainly localized in the Golgi and immature secretory vesicles (49,50,67), no colocalization between Syt VII-GFP and Syt IV was observed even in the tips of the cellular processes (I, inset, arrow) or in the perinuclear region. Confocal images were taken to highlight the localization of Syt VII-GFP in the tips of the cellular processes (i.e.…”

Section: Construction Of Psilencer-syt VII Vectors For Syt Vii Silencsupporting

confidence: 86%

Synaptotagmin VII Is Targeted to Dense-core Vesicles and Regulates Their Ca2+-dependent Exocytosis in PC12 Cells

Fukuda

Kanno

Satoh

et al. 2004

Journal of Biological Chemistry

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Section: Construction Of Psilencer-syt VII Vectors For Syt Vii Silencsupporting

confidence: 86%

Synaptotagmin VII Is Targeted to Dense-core Vesicles and Regulates Their Ca2+-dependent Exocytosis in PC12 Cells

Fukuda

Kanno

Satoh

et al. 2004

Journal of Biological Chemistry

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“…As shown in Fig. 2A, [ 35 S]Syt I was retained by an immobilized N-TRPV1-His fusion protein. Similarly, Syt I was preferentially bound to the core ankyrin repeats.…”

Section: Syt IX and Snapin Interact With The N Terminus Of Trpv1-mentioning

confidence: 84%

“…5, C, D, and F). Because it has been shown that overexpression of SNARE proteins may abrogate SNARE-dependent exocytosis (35), this finding suggests that TRPV1 potentiation by PKC may occur partly by the rapid recruitment of vesicle-associated channel molecules to the cell surface by exocytosis.…”

Section: Fig 6 Potentiation Of Trpv1 Activity By Mglur5 Activationmentioning

confidence: 98%

“…To verify that Snapin and Syt IX bind directly to the N terminus of TRPV1 and to determine the interacting domain on the channel, hexahistidine-tagged fusion proteins of wild type (N-TRPV1-His) and N-TRPV1 deletion mutants were immobilized on nickel-agarose beads and incubated with in vitro translated [ 35 the three ankyrin repeats notably weakened the interaction, although it did not completely abrogate it, suggesting that neighboring domains may contribute to protein binding. These data demonstrate that Snapin and Syt IX strongly interact in vitro with the N-TRPV1.…”

Section: Syt IX and Snapin Interact With The N Terminus Of Trpv1-mentioning

confidence: 99%

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Regulated Exocytosis Contributes to Protein Kinase C Potentiation of Vanilloid Receptor Activity

Morenilla‐Palao

Planells-Cases

García-Sanz

et al. 2004

Journal of Biological Chemistry

392

302

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The vanilloid receptor-1 (TRPV1) plays a key role in the perception of peripheral thermal and inflammatory pain. TRPV1 expression and channel activity are notably up-regulated by proalgesic agents. The transduction pathways involved in TRPV1 sensitization are still elusive. We have used a yeast two-hybrid screen to identify proteins that associate with the N terminus of TRPV1. We report that two vesicular proteins, Snapin and synaptotagmin IX (Syt IX), strongly interact in vitro and in vivo with the TRPV1 N-terminal domain. In primary dorsal root ganglion neurons, TRPV1 co-distributes in vesicles with Syt IX and the vesicular protein synaptobrevin. Neither Snapin nor Syt IX affected channel function, but they notably inhibited protein kinase C (PKC)-induced potentiation of TRPV1 channel activity with a potency that rivaled the blockade evoked by botulinum neurotoxin A, a potent blocker of neuronal exocytosis. Noteworthily, we found that PKC activation induced a rapid delivery of functional TRPV1 channels to the plasma membrane. Botulinum neurotoxin A blocked the TRPV1 membrane translocation induced by PKC that was activated with a phorbol ester or the metabotropic glutamate receptor mGluR5. Therefore, our results indicate that PKC signaling promotes at least in part the SNARE-dependent exocytosis of TRPV1 to the cell surface. Taken together, these findings imply that activitydependent delivery of channels to the neuronal surface may contribute to the buildup and maintenance of thermal inflammatory hyperalgesia in peripheral nociceptor terminals.TRPV1 1 is a capsaicin-, proton-and heat-sensitive, cationselective ion channel expressed in nociceptors that participates in the transduction of noxious chemical and thermal stimuli by sensory nerve endings in peripheral tissues (1-3). Heterologous expression of TRPV1 cDNA results in ionic currents that recapitulate most of the functional properties displayed by native capsaicin-and heat-activated currents in sensory neurons (1, 2). For instance, TRPV1 exhibits a time-and Ca 2ϩ -dependent desensitization, a long lasting refractory state during which the receptor does not respond to vanilloids or other stimuli (2). In addition, the channel activity of TRPV1 is remarkably upregulated by inflammatory mediators through the activation of phospholipase C and protein kinases A and C (PKA and PKC) signaling pathways (4 -13). Recent evidence shows that an increase in TRPV1 expression in peripheral nociceptors is critical for the maintenance of inflammatory hyperalgesia (14, 15). The involvement of TRPV1 in heat hypersensitivity is further underscored by the reduced sensitivity of mice lacking TRPV1 (16, 17) and by mice treated with receptor-specific antagonists (18).TRPV1 belongs to the family of transient receptor potential channels, which structurally resembles the family of voltagegated potassium or cyclic nucleotide-gated channels (19). Accordingly, these channels are presumed to be tetrameric assemblies of identical subunits (Fig. 1A), although heteromeric assemblies have be...

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“…The formation of secretory granules is thought to be a signal mediated process, with roles proposed for small GTP-binding proteins, heterotrimeric G proteins, protein phosphorylation and dephosphorylation, and phospholipase D (Austin and Shields, 1997;Urbe et al, 1997;Ktistakis, 1998;Tooze, 1998). As granules mature, they acquire responsiveness to secretagogue (Mains and Eipper, 1981;Arvan et al, 1991), a process that involves removal of specific proteins (Kuliawat et al, 1997;Eaton et al, 2000).…”

Section: Signaling Through P-cip2 Allows Pam To Affect Trafficking Inmentioning

confidence: 99%

Signaling Mediated by the Cytosolic Domain of Peptidylglycine α-Amidating Monooxygenase

Alam

Steveson

Johnson

et al. 2001

MBoC

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The luminal domains of membrane peptidylglycine ␣-amidating monooxygenase (PAM) are essential for peptide ␣-amidation, and the cytosolic domain (CD) is essential for trafficking. Overexpression of membrane PAM in corticotrope tumor cells reorganizes the actin cytoskeleton, shifts endogenous adrenocorticotropic hormone (ACTH) from mature granules localized at the tips of processes to the TGN region, and blocks regulated secretion. PAM-CD interactor proteins include a protein kinase that phosphorylates PAM (P-CIP2) and Kalirin, a Rho family GDP/GTP exchange factor. We engineered a PAM protein unable to interact with either P-CIP2 or Kalirin (PAM-1/K919R), along with PAM proteins able to interact with Kalirin but not with P-CIP2. AtT-20 cells expressing PAM-1/K919R produce fully active membrane enzyme but still exhibit regulated secretion, with ACTH-containing granules localized to process tips. Immunoelectron microscopy demonstrates accumulation of PAM and ACTH in tubular structures at the trans side of the Golgi in AtT-20 cells expressing PAM-1 but not in AtT-20 cells expressing PAM-1/K919R. The ability of PAM to interact with P-CIP2 is critical to its ability to block exit from the Golgi and affect regulated secretion. Consistent with this, mutation of its P-CIP2 phosphorylation site alters the ability of PAM to affect regulated secretion. INTRODUCTIONAtT-20 corticotrope tumor cells have long served as a reliable model system for studying the biosynthesis, storage, and regulated secretion of pituitary peptide hormones (Mains and Eipper, 1978;Moore and Kelly, 1986;Tooze and Tooze, 1986). Cleavage of endogenous pro-opiomelanocortin (POMC) by PC1 (PC1) and carboxypeptidase E yields both adrenocorticotropic hormone (ACTH) and ␤-lipotropin (Fricker and Devi, 1993;Zhou et al., 1993). Production of other POMC peptides requires the action of peptidylglycine ␣-amidating monooxygenase (PAM) (Eipper et al., 1986). Although levels of PAM in AtT-20 cells are 20-fold lower than in the anterior pituitary, complete amidation of POMCderived products occurs (Eipper et al., 1986).PAM is one of the few peptide-processing enzymes that spans the secretory granule membrane. The fact that its luminal, catalytic domains are pH sensitive and are further activated on cleavage from the membrane (Husten and Eipper, 1991;Husten et al., 1993) raised the possibility that PAM might play a role in signaling luminal conditions to the cytosolic machinery involved in secretory granule formation. This type of signaling is essential in communicating information about events occurring in the lumen of the endoplasmic reticulum to cytosolic proteins (Pahl and Baeuerle, 1997;Shamu, 1997;Brown and Goldstein, 1998), as well as in cargo selection during vesicle budding (Kuehn and Herrmann, 1998).We were surprised to find that expression of exogenous PAM in AtT-20 cells at levels equivalent to those in the anterior pituitary blocked the regulated secretion of ACTH, Abbreviations used: ACTH, adrenocorticotropic hormone; DC, COOH-terminal domain of PAM; CHO, C...

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Biogenesis of Regulated Exocytotic Carriers in Neuroendocrine Cells

Cited by 111 publications

References 29 publications

Synaptotagmin VII Is Targeted to Dense-core Vesicles and Regulates Their Ca2+-dependent Exocytosis in PC12 Cells

Synaptotagmin VII Is Targeted to Dense-core Vesicles and Regulates Their Ca2+-dependent Exocytosis in PC12 Cells

Regulated Exocytosis Contributes to Protein Kinase C Potentiation of Vanilloid Receptor Activity

Signaling Mediated by the Cytosolic Domain of Peptidylglycine α-Amidating Monooxygenase

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