Functional analysis of axonal transport vesicles containing APP, APLP1 or APLP2

• Applicant: Professor Dr. Stefan Kins
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2002 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5385113

Axonal transport emerge to represent a common feature in the etiology of several neurodegenerative diseases, such as Huntington's disease, Parkinson's disease, frontotemporal dementia, Creutzfeldt-Jacob disease and Alzheimer's disease (AD). Pathologically, AD is characterized by neurodegeneration, intracellular neurofibrillary tangles and extracellular plaques composed mainly of the beta Amyloid peptide, derived from the amyloid precurser protein (APP). Recent evidence suggests that APP mediates axonal transport, since a function for APP as membrane receptors of the motor protein kinesin-I was postulated. We want to determine if the APP-like proteins APLP1 and APLP2, which are expected to have a similar function, also mediate transport and interact with components of the kinesin motor protein complex. Certain proteins seem to be transported along the axon specifically in those vesicles designated by APP, suggesting in regard to the postulated ovelapping functions of the APP-family members, that APLP1 and APLP2 mediate the transport of another class of vesicles containing identical but also unique cargo proteins. The identification of these cargo proteins is our major goal. These analyses will help to clarify the function of APP-family members under physiological conditions and in the pathology of AD.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1085: Cellular Mechanisms of Alzheimer's Disease
• Participating Person: Professor Dr. Konrad Beyreuther