The Calcium-Binding Protein EFhd2 Modulates Synapse Formation In Vitro and Is Linked to Human Dementia

Eva Borger, Abigail Herrmann, David A Mann, Tara Spires-Jones, Frank Gunn-Moore*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

EFhd2 is a calcium-binding adaptor protein that has been found to be associated with pathologically aggregated tau in the brain in Alzheimer disease and in a mouse model of frontotemporal dementia. EFhd2 has cell type-specific functions, including the modulation of intracellular calcium responses, actin dynamics, and microtubule transport. Here we report that EFhd2 protein and mRNA levels are reduced in human frontal cortex tissue affected by different types of dementia with and without tau pathology. We show that EFhd2 is mainly a neuronal protein in the brain and is abundant in the forebrain. Using short hairpin RNA-mediated knockdown of EFhd2 expression in cultured cortical neurons, we demonstrate that loss of EFhd2 affects the number of synapses developed in vitro whereas it does not alter neurite outgrowth per se. Our data suggest that EFhd2 is involved in the control of synapse development and maintenance through means other than affecting neurite development. The changes in expression levels observed in human dementias might, therefore, play a significant role in disease onset and progression of dementia, which is characterized by the loss of synapses.

Original languageEnglish
Pages (from-to)1166-1182
Number of pages17
JournalJournal of Neuropathology and Experimental Neurology
Volume73
Issue number12
DOIs
Publication statusPublished - Dec 2014

Keywords

  • Alzheimer disease
  • Cortical neurons
  • EFhd2
  • Frontotemporal dementia
  • Frontotemporal lobar degeneration
  • Swiprosin-1
  • Synapses
  • CYCLIN-DEPENDENT KINASE-5
  • ALZHEIMERS-DISEASE
  • AMYLOID-BETA
  • NEUROFIBRILLARY DEGENERATION
  • HIPPOCAMPAL-NEURONS
  • PARKINSONS-DISEASE
  • MOUSE MODELS
  • TAU-PROTEIN
  • PHOSPHORYLATION
  • ACCUMULATION

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