IAS Benjamin Meaker Visiting Professor Maria-Paz Marzolo, Pontificia Universidad Catolica de Chile, Chile

maria-paz marzolo

Defining the SNX17-retriever pathway in endosomal recycling of ApoER2 and reelin signalling

1 August - 27 October 2017

Dr. María Paz Marzolo is an internationally recognised molecular cell biologist, currently working as Associate Professor within the Department of Cellular and Molecular Biology at the Pontificia Universidad Católica de Chile (PUC).

Biography

As a postdoctoral fellow Dr Marzolo worked in the Neurobiology Unit with Dr. Nibaldo Inestrosa in the PUC, and with Dr. Guojun Bu in the Washington University School of Medicine, USA. During this period, Dr. Marzolo studied the expression and function of low-density lipoprotein receptor (LDL-R) in microglia.

On establishing her independent laboratory in 1999 (back at the University of Chile) she expanded her studies into the intracellular trafficking of LDL-R, including LRP1, megalin/LRP2 and ApoER2. Using cell lines, primary culture neurons and animal models, Dr. Marzolo has help to define the cellular machinery involved in the trafficking of these receptors and how this impacts on their roles in neuronal function and metabolic diseases.

Summary

During her sabbatical Dr. Marzolo will be working with Professor Peter Cullen from the School of Biochemistry. Recently, the Cullen laboratory has discovered a multi-protein assembly (that they have termed ‘retriever’) that orchestrates endolysosomal sorting of numerous integral membrane proteins. With evidence that retriever is perturbed in a number of neurodegenerative diseases, Dr. Marzolo is exploring whether retriever regulates ApoER2 transport and more importantly, whether the function of retriever impacts on the reelin signaling pathway and hence participates in central nervous system development and functions in the adult brain. Defining the role of retriever in this specific context will be of great interest to the field of neuroscience. 

During her stay in Bristol, Dr Marzolo will be hosted by Professor Pete Cullen, Biochemistry

Dr Marzolo will be delivering the following seminars during her visit, dates and times to be confirmed:

1. School Lecture, 

Thursday 5 October, 1 PM, C42, Biomedical Sciences Building, University Walk

The role of reelin and ApoER2 signalling networks in the mammalian central nervous system.

Synopsis: Reelin is a large extracellular matrix protein that plays an important role in the mammalian central nervous system (CNS) both during development through neurogenesis, neuronal polarization and neuronal migration, and in the adult in the process of synaptic plasticity during learning and memory. Dysfunctions in reelin signaling are associated with brain lamination defects such as lissencephaly, neuropsychiatric diseases / disorders including autism, schizophrenia and depression, and in the process of neurodegeneration. At the core of reelin’s role is its ability to bind to specific receptors, in particular ApoER2, and to elicit downstream activation of specific signaling pathways. My laboratory has been studying the endocytosis and endosome-to-plasma membrane recycling of the reelin bound ApoER2 in cortical and hippocampal neurons, and how this impacts on the strength and duration of signaling networks that ultimately influence neuronal survival and synaptic activity. During the lecture I will present our latest findings and discuss how these are providing new and exciting insight into the de-regulation of reelin signaling in neurological disease.

2. Graduate Student Seminar:

The neuroprotective role of the endolysosomal network is prevention of age-related neurodegenerative disease.

Synopsis: Efficient sorting and transportation of integral membrane proteins, such as ion channels, nutrient transporters, signalling receptors, cell-cell and cell-matrix adhesion molecules is essential for the function of cellular organelles and hence organism development and physiology. A master orchestrator of integral membrane protein sorting and transport within eukaryotic cells is the endolysosomal network. Subtle de-regulation of cargo sorting through this network is emerging as an important theme in the pathoetiology of neurodegenerative disease including Alzheimer’s disease and Parkinson’s disease. In the seminar I will summarise recent advances in defining the neuroprotective role of the endolysosomal network and how its de-regulation may contribute to neurodegenerative disease.