Ca(2+) signaling occurs via second messenger release from intraorganelle synthesis sites.
Cyclic ADP-ribose is an important Ca(2+)-mobilizing cytosolic messenger synthesized from beta-NAD(+) by ADP-ribosyl cyclases (ARCs). However, the focus upon ectocellular mammalian ARCs (CD38 and CD157) has led to confusion as to how extracellular enzymes generate intracellular messengers in response...
| Hoofdauteurs: | , , , , , , , , , |
|---|---|
| Formaat: | Journal article |
| Taal: | English |
| Gepubliceerd in: |
2008
|
| _version_ | 1826267487922028544 |
|---|---|
| author | Davis, L Morgan, A Ruas, M Wong, J Graeff, R Poustka, A Lee, H Wessel, G Parrington, J Galione, A |
| author_facet | Davis, L Morgan, A Ruas, M Wong, J Graeff, R Poustka, A Lee, H Wessel, G Parrington, J Galione, A |
| author_sort | Davis, L |
| collection | OXFORD |
| description | Cyclic ADP-ribose is an important Ca(2+)-mobilizing cytosolic messenger synthesized from beta-NAD(+) by ADP-ribosyl cyclases (ARCs). However, the focus upon ectocellular mammalian ARCs (CD38 and CD157) has led to confusion as to how extracellular enzymes generate intracellular messengers in response to stimuli. We have cloned and characterized three ARCs in the sea urchin egg and found that endogenous ARCbeta and ARCgamma are intracellular and located within the lumen of acidic, exocytotic vesicles, where they are optimally active. Intraorganelle ARCs are shielded from cytosolic substrate and targets by the organelle membrane, but this barrier is circumvented by nucleotide transport. We show that a beta-NAD(+) transporter provides ARC substrate that is converted luminally to cADPR, which, in turn, is shuttled out to the cytosol via a separate cADPR transporter. Moreover, nucleotide transport is integral to ARC activity physiologically because three transport inhibitors all inhibited the fertilization-induced Ca(2+) wave that is dependent upon cADPR. This represents a novel signaling mechanism whereby an extracellular stimulus increases the concentration of a second messenger by promoting messenger transport from intraorganelle synthesis sites to the cytosol. |
| first_indexed | 2024-03-06T20:54:56Z |
| format | Journal article |
| id | oxford-uuid:38df3ed9-4a51-440f-91c7-e9286581e7cb |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:54:56Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:38df3ed9-4a51-440f-91c7-e9286581e7cb2022-03-26T13:52:36ZCa(2+) signaling occurs via second messenger release from intraorganelle synthesis sites.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:38df3ed9-4a51-440f-91c7-e9286581e7cbEnglishSymplectic Elements at Oxford2008Davis, LMorgan, ARuas, MWong, JGraeff, RPoustka, ALee, HWessel, GParrington, JGalione, ACyclic ADP-ribose is an important Ca(2+)-mobilizing cytosolic messenger synthesized from beta-NAD(+) by ADP-ribosyl cyclases (ARCs). However, the focus upon ectocellular mammalian ARCs (CD38 and CD157) has led to confusion as to how extracellular enzymes generate intracellular messengers in response to stimuli. We have cloned and characterized three ARCs in the sea urchin egg and found that endogenous ARCbeta and ARCgamma are intracellular and located within the lumen of acidic, exocytotic vesicles, where they are optimally active. Intraorganelle ARCs are shielded from cytosolic substrate and targets by the organelle membrane, but this barrier is circumvented by nucleotide transport. We show that a beta-NAD(+) transporter provides ARC substrate that is converted luminally to cADPR, which, in turn, is shuttled out to the cytosol via a separate cADPR transporter. Moreover, nucleotide transport is integral to ARC activity physiologically because three transport inhibitors all inhibited the fertilization-induced Ca(2+) wave that is dependent upon cADPR. This represents a novel signaling mechanism whereby an extracellular stimulus increases the concentration of a second messenger by promoting messenger transport from intraorganelle synthesis sites to the cytosol. |
| spellingShingle | Davis, L Morgan, A Ruas, M Wong, J Graeff, R Poustka, A Lee, H Wessel, G Parrington, J Galione, A Ca(2+) signaling occurs via second messenger release from intraorganelle synthesis sites. |
| title | Ca(2+) signaling occurs via second messenger release from intraorganelle synthesis sites. |
| title_full | Ca(2+) signaling occurs via second messenger release from intraorganelle synthesis sites. |
| title_fullStr | Ca(2+) signaling occurs via second messenger release from intraorganelle synthesis sites. |
| title_full_unstemmed | Ca(2+) signaling occurs via second messenger release from intraorganelle synthesis sites. |
| title_short | Ca(2+) signaling occurs via second messenger release from intraorganelle synthesis sites. |
| title_sort | ca 2 signaling occurs via second messenger release from intraorganelle synthesis sites |
| work_keys_str_mv | AT davisl ca2signalingoccursviasecondmessengerreleasefromintraorganellesynthesissites AT morgana ca2signalingoccursviasecondmessengerreleasefromintraorganellesynthesissites AT ruasm ca2signalingoccursviasecondmessengerreleasefromintraorganellesynthesissites AT wongj ca2signalingoccursviasecondmessengerreleasefromintraorganellesynthesissites AT graeffr ca2signalingoccursviasecondmessengerreleasefromintraorganellesynthesissites AT poustkaa ca2signalingoccursviasecondmessengerreleasefromintraorganellesynthesissites AT leeh ca2signalingoccursviasecondmessengerreleasefromintraorganellesynthesissites AT wesselg ca2signalingoccursviasecondmessengerreleasefromintraorganellesynthesissites AT parringtonj ca2signalingoccursviasecondmessengerreleasefromintraorganellesynthesissites AT galionea ca2signalingoccursviasecondmessengerreleasefromintraorganellesynthesissites |