MSc Exit Seminar – Amriya Naufer (Terebiznik lab)

MSc Exit Seminar

Wednesday September 23rd, 1:10 pm – Room MW 229, University of Toronto at Scarborough

Amriya Naufer (Terebiznik lab)

“Phagocytosis of Filamentous Bacteria: Impact of Target Morphology on Phagosomal Maturation”

Abstract

Phagocytosis has primarily been characterized by studies that utilized spheroidal particles as targets. However, phagocytes encounter targets of a disparate morphology in nature. Particles with filamentous morphology can present a hurdle to phagocytosis and yet, our understanding of the cellular mechanisms contributing to this process are limited. For example, during phagocytosis of long filamentous bacterial targets (FT), the nascent phagocytic cups can take more than 30 minutes to be completely internalized. During this time, the phagocytic cup is composed of two distinct domains – the actin-rich domain proximal to the plasma membrane and the internal phagocytic cup, which is embedded within the cytoplasm despite its continuity with the plasma membrane. Interestingly, FT-enclosing phagocytic cups (PCs) can sequentially fuse with endosomes and lysosomes, prior to sealing into a phagosome. Here, we present evidence that PI(3)P, an early endosomal lipid regulator, accumulates significantly at PCs and co-exists with lysosomal protein, LAMP1. Our results indicate that aberrant accumulation of PI(3)P may be a consequence of the neutrality of the compartment on which it is maintained; acidification of phagocytic cups abrogates PI(3)P accumulation at PCs. Remarkably, PI(3)P accumulation was observed to alter significant aspects of the late stage of maturation, primarily evidenced by the delay in late endosomal protein activation. Our findings reveal that key aspects of phagosomal maturation are in fact conditioned by the morphology of the target.