Abstract:
:The dipeptide glycyl-l-phenylalanine 2-naphthylamide (GPN) is widely used to perturb lysosomes because its cleavage by the lysosomal enzyme cathepsin C is proposed to rupture lysosomal membranes. We show that GPN evokes a sustained increase in lysosomal pH (pHly), and transient increases in cytosolic pH (pHcyt) and Ca2+ concentration ([Ca2+]c). None of these effects require cathepsin C, nor are they accompanied by rupture of lysosomes, but they are mimicked by structurally unrelated weak bases. GPN-evoked increases in [Ca2+]c require Ca2+ within the endoplasmic reticulum (ER), but they are not mediated by ER Ca2+ channels amplifying Ca2+ release from lysosomes. GPN increases [Ca2+]c by increasing pHcyt, which then directly stimulates Ca2+ release from the ER. We conclude that physiologically relevant increases in pHcyt stimulate Ca2+ release from the ER in a manner that is independent of IP3 and ryanodine receptors, and that GPN does not selectively target lysosomes.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Atakpa P,van Marrewijk LM,Apta-Smith M,Chakraborty S,Taylor CWdoi
10.1242/jcs.223883subject
Has Abstractpub_date
2019-02-01 00:00:00issue
3eissn
0021-9533issn
1477-9137pii
jcs.223883journal_volume
132pub_type
杂志文章abstract::The development of DNA microarrays to study simultaneously the level of mRNA expressed from thousands of genes offers great promise to cell biologists. Microarrays can be used to gain detailed information about transcriptional changes involved in a specific pathway, potentially leading to the identification of novel c...
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更新日期:2018-06-11 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
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journal_title:Journal of cell science
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journal_title:Journal of cell science
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更新日期:2002-01-01 00:00:00
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journal_title:Journal of cell science
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更新日期:2002-06-01 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:2002-02-15 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.01153
更新日期:2004-06-15 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.166553
更新日期:2015-07-15 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
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journal_title:Journal of cell science
pub_type: 杂志文章,评审
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更新日期:2002-03-15 00:00:00
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pub_type: 杂志文章,评审
doi:
更新日期:2002-06-01 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1997-10-01 00:00:00
abstract::AMP-activated protein kinase (AMPK), a cellular metabolic sensor, is essential in energy regulation and metabolism. Hepatocyte polarization during liver development and regeneration parallels increased metabolism. The current study investigates the effects of AMPK and its upstream activator LKB1 on polarity and bile c...
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pub_type: 杂志文章
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更新日期:2010-10-01 00:00:00
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journal_title:Journal of cell science
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