Nanoscale mapping of the Met receptor on hippocampal neurons by AFM and confocal microscopy

Abstract

Hepatocyte growth factor (HGF), a neurotrophic protein, acting through its tyrosine kinase receptor, Met, facilitates learning and synaptic plasticity. In concert with the role of the HGF/Met system in synaptic plasticity, we demonstrate that Met is localized to brain regions which undergo extensive synaptic remodeling. We demonstrate that Met activation results in an increase in dendritic spine density and functional synapses. Based on these observations, we hypothesized that Met should be associated with post-synaptic elements found on dendritic spines. Thus, the goal of this study was to determine the sub-cellular localization of Met on hippocampal neurons. Using an atomic force microscopy tip decorated with a specific Met antibody, the location of Met was mapped to different cellular compartments of hippocampal pyramidal neurons. Our results indicated that multimeric activated Met was found to be concentrated in the dendritic compartment while the inactivated monomeric form of Met was prominent on the soma.

From the clinical editor: The goal of this study was to determine the sub-cellular localization of Met on hippocampal neurons using nanotechnology-based techniques, using an atomic force microscopy tip decorated with a specific Met antibody. The authors demonstrate that multimeric activated Met was found to be concentrated in the dendritic compartment while the inactivated monomeric form of Met was prominent in the soma of hippocampal pyramidal neurons.