Once and only once: mechanisms of centriole duplication and their deregulation in disease

Abstract

Centrioles are conserved microtubule-based organelles that form the core of the centrosome and act as templates for the formation of cilia and flagella. Centrioles have important roles in most microtubule related processes, including motility, cell division and cell signaling. To coordinate these diverse cellular processes, centriole number must be tightly controlled. In cycling cells, one new centriole is formed next to each preexisting centriole in every cell cycle. Advances in imaging, proteomics, structural biology and genome editing have revealed new insights into centriole biogenesis, how centriole numbers are controlled and how alterations in these structures contribute to diseases such as cancer and neurodevelopmental disorders. Moreover, recent work has uncovered the existence of surveillance pathways that limit proliferation of cells with numerical centriole aberrations. Here we discuss recent progress in this field with a focus on signaling pathways and molecular mechanisms.

Centriolar satellites are acentriolar assemblies of centrosomal proteins

“…A remarkable 82 of the 223 proteins in CS‐WT are known components of the centrosome. Although several factors involved in centriole biogenesis are among these 82 proteins, the three critical proteins that drive centriole formation, SAS‐6, STIL and CEP152 along with PLK4 were absent from CS‐WT (Banterle & Gonczy, ; Nigg & Holland, ). The low detection rates may simply reflect low abundance of these proteins, which is especially relevant because STIL and PLK4 are among the five least abundant proteins at the centrosome according to a recent study (Bauer et al , ).…”

ALMS1 and Alström syndrome: a recessive form of metabolic, neurosensory and cardiac deficits

“…Centrioles are evolutionarily conserved cylindrical structures composed of nine triplet MTs, approximately 500 nm in length [20]. Notably, ALMS1 localises specifically to the base, or proximal end, of these structures [21] (Figs.…”

Structural centrosome aberrations promote non‐cell‐autonomous invasiveness

“…Centrosomes function in the organization of microtubules and in ciliogenesis (Bornens, ; Conduit et al , ; Sanchez & Dynlacht, ; Prosser & Pelletier, ; Nigg & Holland ), and dysfunctions of these organelles have been linked to several human diseases, notably ciliopathies and microcephaly or dwarfism (Nigg & Raff, ; Bettencourt‐Dias et al , ; Braun & Hildebrandt, ). Centrosome aberrations are also prominent in cancers, including pre‐invasive in situ carcinomas (Lingle et al , ; Pihan et al , ; Guo et al , ), suggesting that they contribute actively to carcinogenesis (Lingle et al , ; Nigg, ; Pujana et al , ; Zyss & Gergely, ; Godinho & Pellman, ; Gonczy, ).…”