Hook proteins: association with Alzheimer pathology and regulatory role of hook3 in amyloid beta generation

Lydia Herrmann; Caspar Wiegmann; Annika Arsalan-Werner; Isabel Hilbrich; Carsten Jäger; Katharina Flach; Anne Suttkus; Ingolf Lachmann; Thomas Arendt; Max Holzer

doi:10.1371/journal.pone.0119423

Hook proteins: association with Alzheimer pathology and regulatory role of hook3 in amyloid beta generation

PLoS One. 2015 Mar 23;10(3):e0119423. doi: 10.1371/journal.pone.0119423. eCollection 2015.

Affiliations

¹ Paul Flechsig Institute of Brain Research, Department of Molecular and Cellular Mechanism of Neurodegeneration, University of Leipzig, Leipzig, Germany.
² AJ Roboscreen GmbH, Leipzig, Germany.

Abstract

Defects in intracellular transport are implicated in the pathogenesis of Alzheimer's disease (AD). Hook proteins are a family of cytoplasmic linker proteins that participate in endosomal transport. In this study we show that Hook1 and Hook3 are expressed in neurons while Hook2 is predominantly expressed in astrocytes. Furthermore, Hook proteins are associated with pathological hallmarks in AD; Hook1 and Hook3 are localized to tau aggregates and Hook2 to glial components within amyloid plaques. Additionally, the expression of Hook3 is reduced in AD. Modelling of Hook3 deficiency in cultured cells leads to slowing of endosomal transport and increases β-amyloid production. We propose that Hook3 plays a role in pathogenic events exacerbating AD.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / metabolism*
Alzheimer Disease / pathology*
Amyloid beta-Peptides / metabolism*
Animals
Astrocytes / metabolism
Cell Line
Down-Regulation*
Endosomes / metabolism
Female
HeLa Cells
Humans
Male
Mice
Microtubule-Associated Proteins / genetics
Microtubule-Associated Proteins / metabolism*
Middle Aged
Neurons / metabolism

Substances

Amyloid beta-Peptides
Hook2 protein, human
Microtubule-Associated Proteins
hook1 protein, human
hook3 protein, human

Grants and funding

http://www.dfg.de (HO2368/4-1), http://www.alzheimer-forschung.de (#06825), EU funds (EFRE) of the Sächsische AufbauBank (SAB, 100111005). We acknowledge support from the German Research Foundation (DFG) and University of Leipzig within the program of Open Access Publishing. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.