The calcium-binding protein EFhd2 modulates synapse formation in vitro and is linked to human dementia.
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.
From the School of Biology, University of St. Andrews, St. Andrews (EB, FG-M); Centre for Cognitive and Neural Systems and Euan MacDonald Centre, School of Biomedical Sciences, University of Edinburgh, Edinburgh (AH, TS-J); and Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Salford Royal Hospital, Salford (DAM), United Kingdom.
Eva
E
Borger
Abigail
A
Herrmann
David A
DA
Mann
Tara
T
Spires-Jones
Frank
F
Gunn-Moore
D000818:Animals; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002478:Cells, Cultured; D003704:Dementia / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D051379:Mice; D013569:Synapses / Q000378:metabolism* / Q000473:pathology*
D002135:Calcium-Binding Proteins; C502299:EFHD2 protein, human