SCAMP4 enhances the senescent cell secretome.
Kyoung Mi Kim1, Ji Heon Noh1, Monica Bodogai2
1Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA.
Genes & Development
|July 4, 2018
Summary
Secretory carrier membrane protein 4 (SCAMP4) accumulates on senescent cells, driving the secretion of key senescence-associated secretory phenotype (SASP) factors. This discovery reveals SCAMP4 as a critical regulator of the SASP.
Area of Science:
- Cellular senescence
- Molecular biology
- Biochemistry
Background:
- The senescence-associated secretory phenotype (SASP) is a hallmark of cellular senescence, but its molecular regulators remain largely unknown.
- Senescent cells secrete various factors that influence tissue microenvironments and organismal aging.
Purpose of the Study:
- To identify novel molecular regulators of SASP factor secretion.
- To elucidate the role of secretory carrier membrane protein 4 (SCAMP4) in the SASP.
Main Methods:
- Mass spectrometry was employed to compare protein expression on senescent versus proliferating cells.
- Gene silencing (siSCAMP4) and overexpression techniques were used to manipulate SCAMP4 levels in fibroblasts.
- Quantification of SASP factor secretion (e.g., IL6, IL8, GDF-15, CXCL1, IL7) was performed.
Main Results:
- SCAMP4 was found to be significantly upregulated on the surface of senescent cells.
- Silencing SCAMP4 in senescent cells reduced the secretion of multiple SASP factors.
- Overexpression of SCAMP4 in proliferating cells enhanced SASP factor secretion.
Conclusions:
- SCAMP4 accumulates on senescent cell surfaces and acts as a positive regulator of SASP factor secretion.
- SCAMP4 plays a critical role in promoting the senescence-associated secretory phenotype.
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