Adaptable centriole biogenesis via the intrinsically disordered protein ALMS1.

Abstract

Centriole biogenesis is viewed as a template-free physical transformation where a cartwheel scaffold emerges to guide centriole growth and subsequently disassembles; however, the mechanism underlying cartwheel dynamics remains obscure. Here, we identify the intrinsically disordered protein (IDP) ALMS1 as an external cofactor that causes a seed for cartwheel formation without itself incorporating into the seed structure. The cartwheel seed (CS) forms during interphase as dense composites of CEP152/CEP63 complexes, adopting a nanoscale ring from which the cartwheel grows. Upon mitotic entry, CSs undergo disassembly involving ALMS1, correlating with cartwheel disassembly. Hypomorph ALMS1 mutations trigger aberrant cartwheel expansion-shedding from its own grown centriole, in turn forming ectopic centrioles, leading to perpetual reciprocal amplification. ALMS1 depletion aborts CS assembly, whereas reintroducing ALMS1 initializes biogenesis anew, creating diverse yet heritable centriole architectures that evolve through selection, instead of generating a single canonical form. These findings suggest that centriole biogenesis relies on adaptable transformation cues extrinsic to constituents, propagating via IDP-mediated CS assembly-disassembly cycles, we conjecture, involving memory.