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Cited by 266

The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.

Mechanisms of pH Regulation in the Regulated Secretory Pathway

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Wu, Minnie M., Grabe, Michael, Adams, Stephen, Tsien, Roger Y., Moore, Hsiao-Ping H., Machen, Terry E.·2001·Journal of Biological Chemistry

Abstract

A precise pH gradient between organelles of the regulated secretory pathway is required for sorting and processing of prohormones. We studied pH regulation in live endocrine cells by targeting biotin-based pH indicators to cellular organelles expressing avidin-chimera proteins. In AtT-20 cells, we found that steady-state pH decreased from the endoplasmic reticulum (ER) (pH(ER) = 7.4 +/- 0.2, mean +/- S.D.) to Golgi (pH(G) = 6.2 +/- 0.4) to mature secretory granules (MSGs) (pH(MSG) = 5.5 +/- 0.4). Golgi and MSGs required active H(+) v-ATPases for acidification. ER, Golgi, and MSG steady-state pH values were also dependent upon the different H(+) leak rates across each membrane. However, neither steady-state pH(MSG) nor rates of passive H(+) leak were affected by Cl(-)-free solutions or valinomycin, indicating that MSG membrane potential was small and not a determinant of pH(MSG). Therefore, our data do not support earlier suggestions that organelle acidification is primarily regulated by Cl(-) conductances. Measurements of H(+) leak rates, buffer capacities, and estimates of surface areas and volumes of these organelles were applied to a mathematical model to determine the H(+) permeability (P(H+)) of each organelle membrane. We found that P(H+) decreased progressively from ER to Golgi to MSGs, and proper acidification of Golgi and MSGs required gradual decreases in P(H+) and successive increases in the active H(+) pump density.

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Metadata

Authors
Wu, M. M., Grabe, M., Adams, S., Tsien, R. Y., Moore, H.-P. H., & Machen, T. E.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2001-08
Volume
276
Issue
35
Pages
33027-33035
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2162613182
Cited by
266
References
36
FWCI
4.95
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Mechanisms of pH Regulation in the Regulated Secretory Pathway. https://app.cochat.ai/papers/10.1074/jbc.m103917200
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Wu, M. M., Grabe, M., Adams, S., Tsien, R. Y., Moore, H.-P. H., & Machen, T. E. (2001). Mechanisms of pH Regulation in the Regulated Secretory Pathway. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m103917200

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