Imaging proprotein convertase activities and their regulation in the implanting mouse blastocyst

Axis formation and allocation of pluripotent progenitor cells to the germ layers are governed by the TGF-β-related Nodal precursor and its secreted proprotein convertases (PCs) Furin and Pace4. However, when and where Furin and Pace4 first become active have not been determined. To study the distrib...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of cell biology 2010-10, Vol.191 (1), p.129-139
Main Authors: Mesnard, Daniel, Constam, Daniel B
Format: Article
Language:English
Subjects:
Animals
Biochemistry
Biosensing Techniques
Blastocyst
Blastocyst - enzymology
Cell Lineage
Cell lines
Cell Membrane - metabolism
Cell membranes
Cellular biology
Delta cells
Embryo Implantation
Embryology
Embryonic Development
Embryonic stem cells
Embryos
Female
Furin - metabolism
HEK293 cells
Humans
Imaging
Mice
Mice, Transgenic
Pluripotent stem cells
Proprotein Convertases - metabolism
Proprotein Convertases - physiology
Proteins
Stem cells
Transgenes
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Axis formation and allocation of pluripotent progenitor cells to the germ layers are governed by the TGF-β-related Nodal precursor and its secreted proprotein convertases (PCs) Furin and Pace4. However, when and where Furin and Pace4 first become active have not been determined. To study the distribution of PCs, we developed a novel cell surface-targeted fluorescent biosensor (cell surface-linked indicator of proteolysis [CLIP]). Live imaging of CLIP in wild-type and Furin- and Pace4-deficient embryonic stem cells and embryos revealed that Furin and Pace4 are already active at the blastocyst stage in the inner cell mass and can cleave membrane-bound substrate both cell autonomously and nonautonomously. CLIP was also cleaved in the epiblast of implanted embryos, in part by a novel activity in the uterus that is independent of zygotic Furin and Pace4, suggesting a role for maternal PCs during embryonic development. The unprecedented sensitivity and spatial resolution of CLIP opens exciting new possibilities to elucidate PC functions in vivo.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.201005026