DNAJC7 expression in rat brain after a single cortical injury and in human ALS-affected brain cortex and hippocampus

DNAJC7 is a highly conserved J-domain protein that recently was determined to have mutations in amyotrophic lateral sclerosis (ALS). The expression of DNAJC7 in the nervous system is not well known, nor is if DNAJC7 has a role in injury. Here we characterize the expression of DNAJC7 in a rat model of traumatic brain injury in which the temporal cascade of events leading to tau pathology has been mapped. DNAJC7 expression increases after injury, with expression in neurons, astrocytes and microglia. After injury, expression selectively decreases in granular cells of CA2 in the hippocampus, and localization in neurons in the cortex moves from perikaryal into cell processes. DNAJC7 also localizes to phospho-Thr175 tau and TNT1 positive (exposed PAD) tau but dissociates rapidly from PAD exposed tau suggesting that structural change may play a role in its release. In vitro a phospho-Thr175 tau mimic (Thr175Asp) failed to immunoprecipitate DNAJC7, while phospho-null (Thr175Ala) and wildtype tau did, suggesting this phosphoresidue is likely less important for dissociation than the subsequent structural change in tau. Human brain (cortex and hippocampus from neuropathologically normal controls, ALS and ALS with cognitive impairment) was also examined for DNAJC7 expression and tau interaction. DNAJC7 expression was altered in all ALS cases with localization in cell processes, and nuclear expression in oligodendrocytes, while in only ALS cases with cognitive impairment many additional large arborized cells in the cortex and hippocampus appear to have increased DNAJC7 expression in cell processes. Wasteosomes (corpora amylacea) were also DNAJC7 positive. Taken together, DNAJC7 expression in the brain is widespread, is altered in a rat model of brain injury and in ALS and ALSci, and its dissociation from tau appears to be during or shortly after PAD exposure.