Back to Search
Start Over
A reverse signaling pathway downstream of Sema4A controls cell migration via Scrib.
- Source :
-
The Journal of cell biology [J Cell Biol] 2017 Jan 02; Vol. 216 (1), pp. 199-215. Date of Electronic Publication: 2016 Dec 22. - Publication Year :
- 2017
-
Abstract
- Semaphorins comprise a large family of ligands that regulate key cellular functions through their receptors, plexins. In this study, we show that the transmembrane semaphorin 4A (Sema4A) can also function as a receptor, rather than a ligand, and transduce signals triggered by the binding of Plexin-B1 through reverse signaling. Functionally, reverse Sema4A signaling regulates the migration of various cancer cells as well as dendritic cells. By combining mass spectrometry analysis with small interfering RNA screening, we identify the polarity protein Scrib as a downstream effector of Sema4A. We further show that binding of Plexin-B1 to Sema4A promotes the interaction of Sema4A with Scrib, thereby removing Scrib from its complex with the Rac/Cdc42 exchange factor βPIX and decreasing the activity of the small guanosine triphosphatase Rac1 and Cdc42. Our data unravel a role for Plexin-B1 as a ligand and Sema4A as a receptor and characterize a reverse signaling pathway downstream of Sema4A, which controls cell migration.<br /> (© 2017 Sun et al.)
- Subjects :
- Animals
Genotype
HEK293 Cells
HeLa Cells
Humans
Intracellular Signaling Peptides and Proteins genetics
Mass Spectrometry
Membrane Proteins genetics
Mice, Inbred C57BL
Mice, Knockout
Neoplasm Invasiveness
Neoplasms genetics
Neoplasms pathology
Nerve Tissue Proteins metabolism
Phenotype
RNA Interference
Receptors, Cell Surface metabolism
Rho Guanine Nucleotide Exchange Factors metabolism
Semaphorins deficiency
Semaphorins genetics
Time Factors
Transfection
Tumor Suppressor Proteins genetics
cdc42 GTP-Binding Protein metabolism
rac GTP-Binding Proteins metabolism
Cell Movement
Dendritic Cells metabolism
Intracellular Signaling Peptides and Proteins metabolism
Membrane Proteins metabolism
Neoplasms metabolism
Semaphorins metabolism
Signal Transduction
Tumor Suppressor Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1540-8140
- Volume :
- 216
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 28007914
- Full Text :
- https://doi.org/10.1083/jcb.201602002