Localization of phosphotyrosine adaptor protein ShcD/SHC4 in the adult rat central nervous system

Hannah N Robeson,Laura A New,John N Armstrong,Hayley R Lau,Nina Jones,Jasmin Lalonde

doi:10.1186/s12868-019-0541-5

Abstract

BackgroundMammalian Shc (Src homology and collagen) proteins comprise a family of four phosphotyrosine adaptor molecules which exhibit varied spatiotemporal expression and signaling functions. ShcD is the most recently discovered homologue and it is highly expressed in the developing central nervous system (CNS) and adult brain. Presently however, its localization within specific cell types of mature neural structures has yet to be characterized.ResultsIn the current study, we examine the expression profile of ShcD in the adult rat CNS using immunohistochemistry, and compare with those of the neuronally enriched ShcB and ShcC proteins. ShcD shows relatively widespread distribution in the adult brain and spinal cord, with prominent levels of staining throughout the olfactory bulb, as well as in sub-structures of the cerebellum and hippocampus, including the subgranular zone. Co-localization studies confirm the expression of ShcD in mature neurons and progenitor cells. ShcD immunoreactivity is primarily localized to axons and somata, consistent with the function of ShcD as a cytoplasmic adaptor. Regional differences in expression are observed among neural Shc proteins, with ShcC predominating in the hippocampus, cerebellum, and some fiber tracts. Interestingly, ShcD is uniquely expressed in the olfactory nerve layer and in glomeruli of the main olfactory bulb.ConclusionsTogether our findings suggest that ShcD may provide a distinct signaling contribution within the olfactory system, and that overlapping expression of ShcD with other Shc proteins may allow compensatory functions in the brain.

Highlights

Mammalian Shc (Src homology and collagen) proteins comprise a family of four phosphotyrosine adaptor molecules which exhibit varied spatiotemporal expression and signaling functions
Shc proteins are characterized by the presence of an amino-terminal phosphotyrosine binding (PTB) domain, a central collagen homology 1 (CH1) region which contains a series of phosphorylatable tyrosine residues, and a carboxy-terminal Src homology 2 (SH2) domain
ShcD deviates from the other Shc proteins with an additional 3 tyrosine residues in the CH1 region and loss of the Robeson et al BMC Neurosci (2019) 20:57 central adaptin binding motif, which impacts trafficking of the EGFR [9]

Summary

Introduction

Mammalian Shc (Src homology and collagen) proteins comprise a family of four phosphotyrosine adaptor molecules which exhibit varied spatiotemporal expression and signaling functions. The Shc (Src homology and collagen) family of adaptor molecules plays an important role in mediating signaling events that link activated cell surface proteins such as receptor tyrosine kinases (RTKs) to intracellular signaling pathways [1]. Shc proteins are characterized by the presence of an amino-terminal phosphotyrosine binding (PTB) domain, a central collagen homology 1 (CH1) region which contains a series of phosphorylatable tyrosine residues, and a carboxy-terminal Src homology 2 (SH2) domain. The four identified members of the Shc family are ShcA/Shc/SHC1 [3], ShcB/Sli/SHC2 [4], ShcC/Rai/NShc/SHC3 [4,5,6], and the most recently discovered and least-characterized homologue, ShcD/SHC4 or RaLP (Rai-like protein) [7, 8]. ShcD deviates from the other Shc proteins with an additional 3 tyrosine residues in the CH1 region and loss of the Robeson et al BMC Neurosci (2019) 20:57 central adaptin binding motif, which impacts trafficking of the EGFR [9]

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Results

Discussion

Conclusion