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My independent career started at the University of Chile in 1999, studying the expression and functions of LRP1 and the mannose receptor in microglia (JNR 1999, 2000). In 2002, I moved to the P. Catholic University of Chile. The laboratory has been deciphering the function and intracellular trafficking of large endocytic receptors from the low-density lipoprotein receptor (LDL-R) family, including LRP1, megalin/LRP2, and ApoER2. These are multifunctional receptors of a variety of ligands with relevant physiological functions. Using cell lines, neurons in primary culture, and animal models, we study the sorting signals, exocytic and endocytic pathways, the cellular machinery involved in the receptors ́trafficking and their roles associated with neuronal function and regeneration as well to metabolic diseases (Sem Dev Biol 2009; Biol Res 2011; Frontiers in Biol 2012; Biochem J. 2017). As a result of these studies, we have shown the existence of an apical sorting signal in the cytoplasmic domain of type one membrane protein, as is the case for Megalin. The receptor's role in kidney and megalin reduction is associated with different diseases, including Lowe Syndrome, resulting in impaired endosomal recycling (EMBO J 2011; Frontiers in Cell and Dev Biol, 2022). Besides, megalin recycling is negatively regulated by the phosphorylation of its tail, mediated by GSK3 (Traffic 2007). Megalin expression is positively regulated by FXR (JLR 2004) and PPAR alpha and gamma (PLosOne 2011) and negatively by TGF-beta (PlosOne 2019). We found that megalin is expressed in the gallbladder and could be protective in gallstone disease, a frequent pathology in Chile (JLR 2004). Moreover, we have also described basolateral/somatodendritic sorting and recycling signals in LRP1 (Traffic 2003, MBoC 2009; Traffic 2013). LRP1 trafficking is regulated by the adaptor complex AP1B, the endosomal protein SNX17 (MBoC 2009), and Protein Kinase D (JNS 2008). We are now focused on studying ApoER2, the receptor participating in the Reelin signaling pathway. ApoER2 trafficking is relevant to reelin signaling, and this pathway accomplishes relevant roles in the central and peripheral nervous systems. In particular, we are interested in determining how reelin signaling impacts membrane trafficking and cell migration and how ApoER2 trafficking is influenced by ligand binding. We have demonstrated that ApoER2 follows a clathrin-dependent internalization (Traffic 2005). Its endosomal recycling and signaling are regulated by SNX17 (PlosOne 2014), and ApoER2 function is also regulates APP trafficking and processing (Mol Neurodeg 2007). ApoER2/reelin regulates PNS regeneration, favoring Schwann cell migration (MCN 2015) and axonal extension (J. Neurosci Res, 2020). We recently collaborated with Dr. Campusano at PUC to study the role of Drosophila melanogaster´s lipophorin receptors in mushroom body development and function (BMC Biology, 2022).
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Papers共 77 篇Author StatisticsCo-AuthorSimilar Experts
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Maria-Paz Marzolo, Carlos Alarcon, Mario Caracci,Hector Pizarro,Luz M. Fuentealba,Raffaella De Pace,Juan S. Bonifacino,Gonzalo Mardones
JOURNAL OF NEUROCHEMISTRY (2023): 100-100
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Mario O. Caracci,Héctor Pizarro, Carlos Alarcón-Godoy,Luz M. Fuentealba,Pamela Farfán,Raffaella De Pace,Natacha Santibañez,Viviana A. Cavieres, Tammy P. Pástor,Juan S. Bonifacino,Gonzalo A. Mardones,María-Paz Marzolo
bioRxiv (2021)
PEPTIDES (2021): 170646-170646
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#Papers: 77
#Citation: 3147
H-Index: 34
G-Index: 54
Sociability: 5
Diversity: 3
Activity: 20
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