Centriole-Associated Fate Determinants (CAFDs)
DOI:
https://doi.org/10.65649/5h3cpa69Keywords:
Centrosome, Cell Fate, Asymmetric Division, Stem Cells, Cilium, Signaling, CentriolopathiesAbstract
Emerging evidence, however, reveals that this organelle plays a far more expansive role as a dynamic platform for cell fate determination. We propose the concept of Centriole-Associated Fate Determinants (CAFDs)—a class of biomolecules, including proteins, RNAs, and ribonucleoprotein complexes, that physically localize to the centriole or pericentriolar material and whose function in specifying cell identity is directly modulated by this association. Unlike core structural components, CAFDs are "guests" at the centriole, with primary biochemical roles in transcription, signaling, translation, or proteostasis. This review provides a comprehensive framework for understanding CAFDs, including their conceptual basis, classification by chemical nature and mechanism of action, and a detailed catalogue of key examples across model systems. We examine the regulatory mechanisms that control CAFD activity at the centriole—post-translational modifications, conformational changes, competitive binding, and signal-dependent release—and survey the advanced methodologies for their identification and study, from proximity-dependent biotinylation to super-resolution imaging and induced tethering. An evolutionary perspective reveals that primitive CAFD-like functions likely originated in unicellular eukaryotes to coordinate life cycle transitions, later co-opted in metazoans for asymmetric division and differentiation. Disruption of CAFDs or their centriolar adapters underlies a spectrum of human pathologies, including microcephaly, ciliopathies, and cancer. We conclude with an integrative model positioning the centriole as a strategic command post that integrates cytoskeletal architecture with gene regulatory programs, and pose the central question for future therapeutic exploration: Can cell fate be controlled by pharmacologically modulating specific CAFD-centriole interactions?
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