PUBLICATION

Common themes in PrP signaling: the Src remains the same

Authors
Ochs, K., Málaga-Trillo, E.
ID
ZDB-PUB-141105-7
Date
2014
Source
Frontiers in cell and developmental biology   2: 63 (Other)
Registered Authors
Málaga-Trillo, Edward
Keywords
Src family kinases, endocytosis, ion channels, knockout mice, myelination, prion protein, tyrosine phosphorylation, zebrafish
MeSH Terms
none
PubMed
25364767 Full text @ Front Cell Dev Biol
Abstract
The ability of the cellular prion protein (PrP(C)) to trigger intracellular signals appears central to neurodegeneration pathways, yet the physiological significance of such signals is rather puzzling. For instance, PrP(C) deregulation disrupts phenomena as diverse as synaptic transmission in mammals and cell adhesion in zebrafish. Although unrelated, the key proteins in these events -the NMDA receptor (NMDAR) and E-cadherin, respectively- are similarly modulated by the Src family kinase (SFK) Fyn. These observations highlight the importance of PrP(C)-mediated Fyn activation, a finding reported nearly two decades ago. Given their complex functions and regulation, SFKs may hold the key to intriguing aspects of PrP biology such as its seemingly promiscuous functions and the lack of strong phenotypes in knockout mice. Here we provide a mechanistic perspective on how SFKs might contribute to the uncertain molecular basis of neuronal PrP phenotypes affecting ion channel activity, axon myelination and olfactory function. In particular, we discuss SFK target proteins involved in these processes and the role of tyrosine phosphorylation in the regulation of their activity and cell surface expression.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping