Regulation and function of specialized membrane protrusions in intercellular communication

Cells use specialized membrane extensions that enable the exchange of signals, organelles and other cargo to support long-range communication within complex tissues. Among these, tunnelling nanotubes, cytonemes and migrasomes have emerged as key contributors to development, immune responses and disease. Growing evidence has revealed that these structures are more prevalent and functionally diverse than previously appreciated, prompting a re-evaluation of how cells coordinate behaviour across space. In this Review, we discuss recent advances in understanding the formation, regulation and specificity of these dynamic connections, with an emphasis on tunnelling nanotubes and cytonemes, and highlight common principles underlying their architecture and cargo transfer. We further explore how their dysregulation contributes to pathology, underscoring the need to integrate these structures into current models of tissue organization.