Nandakumar, S.; Vasudevan, D.

Cells in metabolically active tissues with high biosynthetic and secretory demands often use robust stress-responsive mechanisms to maintain endoplasmic reticulum (ER) homeostasis. Coordinating such robust stress response mechanisms requires intercellular communication and coordination. Such modalities of intercellular communication have been relatively understudied in the context of stress tolerance. Here, we use the Drosophila melanogaster third instar fat body to demonstrate that adipocytes communicate with each other through intercellular bridges called ring canals to buffer endoplasmic reticulum stress. The fat body supports the exponential growth from embryo to late larval stage over a short period of time through its energy storage and secretory functions, enduring a high basal level of ER stress in the process. We discovered that individual cells in the fat body are paired to one neighboring cell through ring canals. We further demonstrate that ring canals mediate rapid and highly specific intercellular cargo and organellar trafficking, and allow the transport of cytoplasmic, ER-bound and Golgi vesicular proteins. Disrupting fat body ring canals resulted in higher levels of ER stress response markers, aberrant cell size, as well as increased cell lethality in response to exogenous stress. We also find that animals with disrupted fat body ring canals display an overall delay in larval development, likely due to reduced secretion of larval serum proteins from the fat body. In sum, our work reveals a novel feature of intercellular communication in adipose tissue that serves to buffer ER stress across cells which is required for both homeostatic secretory function and maintaining tissue viability under exogenous stress.