Prion Protein at the Leading Edge: Its Role in Cell Motility

Author(s)

Prado, Mariana Brandao ; Melo Escobar, Maria Isabel ; Alves, Rodrigo Nunes ; Coelho, Barbara Paranhos ; Fernandes, Camila Felix de Lima ; Boccacino, Jacqueline Marcia ; Iglesia, Rebeca Piatniczka ; Lopes, Marilene Hohmuth

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 21, n. 18, p. 18-pg., 2020-09-01.

Abstract

Cell motility is a central process involved in fundamental biological phenomena during embryonic development, wound healing, immune surveillance, and cancer spreading. Cell movement is complex and dynamic and requires the coordinated activity of cytoskeletal, membrane, adhesion and extracellular proteins. Cellular prion protein (PrP (c)) has been implicated in distinct aspects of cell motility, including axonal growth, transendothelial migration, epithelial-mesenchymal transition, formation oflamellipodia, and tumor migration and invasion. The preferential location of PrP (c) on cell membrane favors its function as a pivotal molecule in cell motile phenotype, being able to serve as a scaffold protein for extracellular matrix proteins, cell surface receptors, and cytoskeletal multiprotein complexes to modulate their activities in cellular movement. Evidence points to PrP (c) mediating interactions of multiple key elements of cell motility at the intra- and extracellular levels, such as integrins and matrix proteins, also regulating cell adhesion molecule stability and cell adhesion cytoskeleton dynamics. Understanding the molecular mechanisms that govern cell motility is critical for tissue homeostasis, since uncontrolled cell movement results in pathological conditions such as developmental diseases and tumor dissemination. In this review, we discuss the relevant contribution of PrP (c) in several aspects of cell motility, unveiling new insights into both PrP (c) function and mechanism in a multifaceted manner either in physiological or pathological contexts. (AU)

• FAPESP's process: 19/14952-0 - Characterization of intracellular signaling pathways modulated by the cellular prion protein on stemness maintenance in glioblastoma stem cells
• Grantee: Bárbara Paranhos Coelho
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/11097-1 - Modulation of the neural phenotype of glioblastoma stem cells by extracellular miRNA from NSCs
• Grantee: Maria Isabel Melo Escobar
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 19/14741-9 - Study of the role of STI1 and assotiated factors in the proteostasis network and pluripotency regulation
• Grantee: Camila Felix de Lima Fernandes
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 17/26158-0 - Prion protein as stem regulator in glioblastoma stem cells: its role in the formation and function of multiprotein signaling platforms
• Grantee: Mariana Brandão Prado
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 19/12710-9 - Role of cellular prion protein in temozolomide resistance: emphasis on processes modulated by hypoxia
• Grantee: Rebeca Piatniczka Iglesia
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/15557-4 - Prion protein and its partners: emerging targets for glioblastoma stem cell based-therapy
• Grantee: Marilene Hohmuth Lopes
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 20/07450-5 - Evaluation of transcript levels of PrPc downstream targets and intracellular signaling pathways in glioblastoma stem cells
• Grantee: Jacqueline Marcia Boccacino
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 20/04687-4 - The role of neural stem cells extracellular vesicles in the modulation of phenotype of PRNP low and PRNP high glioblastoma stem cells
• Grantee: Rodrigo Nunes Alves
• Support Opportunities: Scholarships in Brazil - Master