Work

Fluorescent Analogue of Batimastat Enables Imaging of α-Secretase in Living Cells

Year: 2015

Type: article

Abstract: The ADAM family of metalloproteases cleave a diverse range of transmembrane substrates, resulting in the release of their soluble ectodomains. This process of protein shedding, termed α-secretase processing, is involved in many facets of both normal and disease related cellular function. While the processing of substrates has been well documented, the regulation and trafficking of the ADAMs are less well understood. Tools that allow for the study of ADAMs under their native environment will allow for a better understanding of their regulation and activity. Here we describe the design and evaluation of a novel fluorescent analogue of a well-characterized ADAM inhibitor, Batimastat. This probe exhibited similar activity for inhibiting α-secretase processing in cells as did Batimastat. Importantly, this probe specifically labeled ADAMs fluorescently in both fixed and living cells, enabling the possibility to study the trafficking of α-secretase proteins in a dynamic environment.

Source: ACS Chemical Neuroscience

DOI: 10.1021/acschemneuro.5b00283

Authors: Geoffray Leriche, Allen C. Chen, Sumin Kim, Dennis J. Selkoe, Jerry Yang

Institutions: University of California San Diego, Brigham and Women's Hospital, Harvard University

Language: English

Topic: Protease and Inhibitor Mechanisms

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Institute on Aging, Air Force Office of Scientific Research