Boston University School of Medicine
Silvio Conte Building, K-123E
72 E. Concord Street
Boston, MA 02118
Lab Phone: 617-638-5074
1997-2001 Diploma in Biology and Ph.D., Institute for Biochemistry II, Medical Faculty of the University of Cologne, Germany
2001-2012 Post-doctoral fellow and research associate, Montreal Neurological Institute, McGill University, Montreal, Canada
|Ian Paolo Mauricio
Receptor trafficking in health and disease
Cells constantly insert and remove receptor proteins at the cell surface to internalize nutrients and signaling molecules and to respond to changes in the extracellular environment. Clathrin-mediated endocytosis is the major receptor internalization route in eukaryotic cells and controls the cell surface levels of numerous receptor classes including nutrient receptors such as transferrin and LDL receptors , signaling receptors such as EGF receptor and other receptor tyrosine kinases (RTKs), and cell-cell and cell-matrix receptors such as cadherins and integrins, respectively. Following internalization, receptors are then sorted through an elaborate, not yet well-understood endosomal system that either allows receptors to enter into a variety of recycling pathways to return to the cell surface, or sorts receptors to lysosomes for degradation. Importantly, receptor sorting is also directly linked to receptor function. For example, growth factor-bound EGF receptor triggers different signaling cascades at the cell surface and on endosomes and in fact, needs to be delivered to lysosomes to terminate signaling events.
Our research focus is to understand how receptor transport controls and drives complex physiological processes. We combine molecular biology, protein biochemistry and cell biology approaches to define the protein machineries and to reveal the mechanisms driving receptor internalization and sorting, spanning the range from studying protein-protein interactions on the amino acid level, over determining the role of these proteins in the internalization and subsequent transport of receptors in various cell systems including neurons, to analyzing the impact of impairing the function of these proteins on physiological processes such as cell migration and differentiation, plasticity, and cell signaling. In particular, we want to understand how endosomal sorting determines the signaling potential of RTKs and how misregulation of these sorting decisions contributes to tumorigenicity and cancer. A second focus is on understanding how changes in the trafficking of receptors for ApoE, an important genetic risk factor for Alzheimer’s disease, affect neuronal function and promote the development and progression of Alzheimer’s disease.
- Interplay between Rab35 and Arf6 controls cargo recycling to coordinate cell adhesion and migration. Allaire PD, Seyed Sadr M, Chaineau M, Seyed Sadr E, Konefal S, Fotouhi M, Maret D, Ritter B, Del Maestro RF, McPherson PS. J Cell Sci. 2013 Feb 1;126(Pt 3):722-31.
- 14-3-3 proteins regulate protein kinase a activity to modulate growth cone turning responses. Kent CB, Shimada T, Ferraro GB, Ritter B, Yam PT, McPherson PS, Charron F, Kennedy TE, Fournier AE. J Neurosci. 2010 Oct 20;30(42):14059-67.
- The p75NTR intracellular domain generated by neurotrophin-induced receptor cleavage potentiates Trk signaling. Ceni C, Kommaddi RP, Thomas R, Vereker E, Liu X, McPherson PS, Ritter B, Barker PA. J Cell Sci. 2010 Jul 1;123(Pt 13):2299-307.
- The Connecdenn DENN domain: a GEF for Rab35 mediating cargo-specific exit from early endosomes. Allaire PD, Marat AL, Dall’Armi C, Di Paolo G, McPherson PS*, Ritter B*. Mol Cell. 2010 Feb 12;37(3):370-82. *co-corresponding author
- The NECAP PHear domain increases clathrin accessory protein binding potential.Ritter B*, Denisov AY*, Philie J, Allaire PD, Legendre-Guillemin V, Zylbergold P, Gehring K, McPherson PS. EMBO J. 2007 Sep 19;26(18):4066-77. Epub 2007 Aug 30. *equal contribution
- Connecdenn, a novel DENN domain-containing protein of neuronal clathrin-coated vesicles functioning in synaptic vesicle endocytosis. Allaire PD, Ritter B, Thomas S, Burman JL, Denisov AY, Legendre-Guillemin V, Harper SQ, Davidson BL, Gehring K, McPherson PS. J Neurosci. 2006 Dec 20;26(51):13202-12.
- Two WXXF-based motifs in NECAPs define the specificity of accessory protein binding to AP-1 and AP-2.Ritter B, Denisov AY, Philie J, Deprez C, Tung EC, Gehring K, McPherson PS. EMBO J. 2004 Oct 1;23(19):3701-10.
- Tandem MS analysis of brain clathrin-coated vesicles reveals their critical involvement in synaptic vesicle recycling. Blondeau F, Ritter B, Allaire PD, Wasiak S, Girard M, Hussain NK, Angers A, Legendre-Guillemin V, Roy L, Boismenu D, Kearney RE, Bell AW, Bergeron JJ, McPherson PS. Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3833-8.
- Identification of a family of endocytic proteins that define a new alpha-adaptin ear-binding motif.Ritter B, Philie J, Girard M, Tung EC, Blondeau F, McPherson PS. EMBO Rep. 2003 Nov;4(11):1089-95.