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Cilia and Extracellular Vesicles are signaling organelles
Author(s) -
Barr Maureen,
Wang Juan,
Silva Malan,
Hall David,
Maguire Julie
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.82.1
Subject(s) - cilium , ciliopathies , biology , intraflagellar transport , microbiology and biotechnology , caenorhabditis elegans , biogenesis , polycystic kidney disease , mechanosensation , flagellum , genetics , phenotype , gene , kidney , receptor , ion channel
Cilia act as a cellular antennae and function in sensation and adhesion (1), with defects resulting in human ciliopathies. EVs act as intercellular signaling parcels that contain and deliver donor cell cargo to recipient cells. EVs mediate a broad range of physiological processes (2‐4). EVs also play diabolical roles in the spread of toxic cargo in cancer, infectious diseases, and neurodegenerative disorders (5, 6). In Chlamydomonas, C. elegans, and mammals, EVs are closely associated with cilia, suggesting that cilia may be essential in EV‐mediated communication as both senders and receivers (7‐13). Despite their profound importance, a fundamental understanding of EV biology and the relationship between cilia and EVs is lacking, including mechanisms regulating EV biogenesis, cargo selection, release, interaction with target cells, and in vivo functions. This knowledge is essential for determining the biological significance of EVs and harnessing their potential therapeutic uses. We have been using the nematode C. elegans to understand the connection between cilia and EVs, and to model human ciliopathies. The C. elegans polycystins (PCs) localize to cilia, providing one of the important first links between the cilium and human disease (14‐16). In humans, the PC‐encoding genes PKD1 and PKD2 are needed for kidney function; loss of PC function leads to Autosomal Dominant Polycystic Kidney Disease (ADPKD, frequency 1/400‐1:1000), one of the most common monogenic diseases (17). Very recently we showed that the C. elegans cilium is a source of bioactive PC‐containing EVs that regulate animal‐to‐animal communication (11). In C. elegans and mammals, PC1 and PC2 act in the same genetic pathway, act in a sensory capacity, localize to cilia, and are contained in secreted EVs (7, 11, 18, 19), indicating ancient conserved functions. By using C. elegans as a springboard to study the fundamental biology of EVs in vivo and the roles of the PCs in cilia and EVs, we hope to advance frontiers of knowledge where very little is known.