With Age Comes Maturity: Biochemical and Structural Transformation of a Human Centriole in the Making

Abstract

Centrioles are microtubule-based cellular structures present in most human cells that build centrosomes and cilia. Proliferating cells have only two centrosomes and this number is stringently maintained through the temporally and spatially controlled processes of centriole assembly and segregation. The assembly of new centrioles begins in early S phase and ends in the third G1 phase from their initiation. This lengthy process of centriole assembly from their initiation to their maturation is characterized by numerous structural and still poorly understood biochemical changes, which occur in synchrony with the progression of cells through three consecutive cell cycles. As a result, proliferating cells contain three structurally, biochemically, and functionally distinct types of centrioles: procentrioles, daughter centrioles, and mother centrioles. This age difference is critical for proper centrosome and cilia function. Here we discuss the centriole assembly process as it occurs in somatic cycling human cells with a focus on the structural, biochemical, and functional characteristics of centrioles of different ages.

TRIM37 prevents formation of centriolar protein assemblies by regulating Centrobin

“…Probably because of such important roles, centriole number is tightly regulated, with most cycling cells having two units at cell cycle onset and four units by the time of mitosis (reviewed in Sullenberger et al, 2020 ). Alterations in centriole number can have adverse consequences on cell physiology and genome integrity.…”

Principal Postulates of Centrosomal Biology. Version 2020

“…The complete process of centrioles maturation from procentriole to mother centriole takes more than one and a half cell cycles in duration [ 36 ]. The exact timing of procentriole initiation is debatable [ 152 ]. The percentage of cells with procentrioles significantly exceeded the S-phase percentage in the cell cycle in synchronized HeLa cells.…”

“…It becomes a daughter centriole after mitosis in the newly formed cell. The centriole becomes a mature mother centriole, acquiring a complete set of its cell activities after the second mitosis in its life [ 36 , 152 ]. The cell (nuclear) cycle and the centriolar (centrosomal) cycle are mutually coordinated ( Figure 4 ) at least at two critical points in the cell cycle: the end of the G1 and the end of the G2 phase [ 13 , 155 ].…”

TRIM37 prevents formation of centriolar protein assemblies by regulating Centrobin stability

“…Centrioles are essential for the formation of cilia and also recruit pericentriolar material (PCM), including the MT nucleator γtubulin ring complex, thus forming the centrosome of animal cells (reviewed in (Bornens, 2012)). Probably because of such important roles, centriole number is tightly regulated, with most cycling cells having two units at the cell cycle onset and four units by the time of mitosis (reviewed in (Sullenberger et al, 2020)).…”

“…whereas the older, mother, centriole is at least two cell generations old, the younger, daughter, centriole was formed in the previous cell cycle. The mother centriole bears distinctive distal and sub-distal appendages that the daughter centriole acquires only later during the cell cycle (reviewed in (Sullenberger et al, 2020)). In human cells, the proximal region of both mother and daughter centrioles in the G1 phase of the cell cycle is encircled by a torus bearing the interacting proteins CEP57/CEP63/CEP152 (Brown et al, 2013;Lukinavicius et al, 2013) (reviewed in (Banterle and Gönczy, 2017)).…”