The role of protein translation and mitochondrial specialization in anchor cell invasion through basement membranes in C. elegans

Abstract

Basement membranes (BM) are dense layers of cross-linked extracellular matrix (ECM) proteins that provide structure for tissues, as well as serving as a barrier that prevents cell movement between tissues. Despite formidable barrier properties, specialized cells have acquired the ability to invade BM during development and physiological homeostasis. Furthermore, dysregulation of invasive behavior is the root of many diseases and disorders. Cell invasion is a robust process that requires extensive signaling, cytoskeletal, and proteolytic proteins to coordinate the physical and chemical removal of BM. Therefore, it is crucial to understand how cells construct, support, and fuel machinery required for invasion. Here, I use the C. elegans anchor cell (AC), an experimentally tractable and visually accessible in vivo model for cell invasion through the BM, to investigate ribosome biogenesis, endomembrane expansion, and mitochondrial specialization in cell invasion through BM. In Chapter 1, I review AC invasion as a model of cell invasion. In Chapter 2, I identified new invasion regulators, an enrichment of ribosomal proteins, and key roles for ribosome biogenesis and endomembrane expansion to meet the heightened protein-translation demands of the cell during invasion through BM. In Chapter 3, I discover that AC basal mitochondria have a specialized electron transport chain (ETC) to produce rapid amounts of ATP to fuel cell invasion and that mitochondrial specialization is dependent on mitochondrial protein import machinery enrichment, cristae remodeling, and mitochondria-endoplasmic reticulum contact sites (MERCS). In Chapter 4, I discuss the implications of these finding on our understanding of how cells construct, support, and fuel machinery required for invasion.