P.8.b.002 Acetylcholine-mediated regulation of secretory cells is associated with calcium release from endoplasmic reticulum via InsPS-sensitive ion channels

AbstractThe metazoan endoplasmic reticulum (ER) serves both as a hub for maturation of secreted proteins and as an intracellular calcium storage compartment, facilitating calcium release-dependent cellular processes. ER calcium depletion robustly activates the unfolded protein response (UPR). However, it is unclear how fluctuations in ER calcium impact organellar proteostasis. Here we report that calcium selectively affects the dynamics of the abundant metazoan ER Hsp70 chaperone BiP, by enhancing its affinity for ADP. In the calcium replete ER, ADP rebinding to post-ATP hydrolysis BiP-substrate complexes competes with ATP binding during both spontaneous and co-chaperone-assisted nucleotide exchange, favouring substrate retention. Conversely, in the calcium depleted ER, relative acceleration of ADP-to-ATP exchange favours substrate release. These findings explain the rapid dissociation of certain substrates from BiP observed in the calcium-depleted ER and suggest a mechanism for tuning ER quality control and coupling UPR activity to signals that mobilise ER calcium in secretory cells.

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Calcium depletion challenges endoplasmic reticulum proteostasis by destabilising BiP-substrate complexes

eLife ◽

10.7554/elife.62601 ◽

2020 ◽

Vol 9 ◽

Author(s):

Steffen Preissler ◽

Claudia Rato ◽

Yahui Yan ◽

Luke A Perera ◽

Aron Czako ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Calcium Release ◽

Atp Hydrolysis ◽

Secretory Cells ◽

Nucleotide Exchange ◽

Calcium Depletion ◽

Er Quality Control ◽

Cellular Processes ◽

The Unfolded Protein Response ◽

Er Calcium

The metazoan endoplasmic reticulum (ER) serves both as a hub for maturation of secreted proteins and as an intracellular calcium storage compartment, facilitating calcium-release-dependent cellular processes. ER calcium depletion robustly activates the unfolded protein response (UPR). However, it is unclear how fluctuations in ER calcium impact organellar proteostasis. Here, we report that calcium selectively affects the dynamics of the abundant metazoan ER Hsp70 chaperone BiP, by enhancing its affinity for ADP. In the calcium-replete ER, ADP rebinding to post-ATP hydrolysis BiP-substrate complexes competes with ATP binding during both spontaneous and co-chaperone-assisted nucleotide exchange, favouring substrate retention. Conversely, in the calcium-depleted ER, relative acceleration of ADP-to-ATP exchange favours substrate release. These findings explain the rapid dissociation of certain substrates from BiP observed in the calcium-depleted ER and suggest a mechanism for tuning ER quality control and coupling UPR activity to signals that mobilise ER calcium in secretory cells.

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Analysis of the Anterior Secretory Cells of Onchidohs Muricata (Nudibranchia)

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100099490 ◽

1981 ◽

Vol 39 ◽

pp. 614-615

Author(s):

Roy Skidmore

Keyword(s):

Endoplasmic Reticulum ◽

Secretory Granules ◽

Golgi Body ◽

The Body ◽

Secretory Cells ◽

Secretory Vesicles ◽

High Magnification ◽

Large Numbers ◽

Membrane Bound ◽

Sole Of The Foot

The long-necked secretory cells in Onchidoris muricata are distributed in the anterior sole of the foot. These cells are interspersed among ciliated columnar and conical cells as well as short-necked secretory gland cells. The long-necked cells contribute a significant amount of mucoid materials to the slime on which the nudibranch travels. The body of these cells is found in the subepidermal tissues. A long process extends across the basal lamina and in between cells of the epidermis to the surface of the foot. The secretory granules travel along the process and their contents are expelled by exocytosis at the foot surface.The contents of the cell body include the nucleus, some endoplasmic reticulum, and an extensive Golgi body with large numbers of secretory vesicles (Fig. 1). The secretory vesicles are membrane bound and contain a fibrillar matrix. At high magnification the similarity of the contents in the Golgi saccules and the secretory vesicles becomes apparent (Fig. 2).

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