TY - JOUR
T1 - Phase Transitioning the Centrosome into a Microtubule Nucleator
AU - Rale, Michael J.
AU - Kadzik, Rachel S.
AU - Petry, Sabine
N1 - Funding Information:
*E-mail: spetry@princeton.edu; phone: 609-258-1553; fax: 609-258-1035. ORCID Michael J. Rale: 0000-0003-1426-6611 Sabine Petry: 0000-0002-8537-9763 Funding This work was supported by the National Institutes of Health (NIH) New Innovator Award, the Pew Scholars Program in the Biomedical Sciences, the David and Lucile Packard Foundation (all to S.P.) and an NIH postdoctoral fellowship 1F32GM119195-01 (to R.S.K.). M.J.R is a Howard Hughes Medical Institute Gilliam Fellow. M.J.R also gratefully acknowledges support as a National Science Foundation (NSF) Graduate Research Fellow. M.J.R was also supported by the National Institute of General Medical Sciences (NIGMS) of the NIH under Grant Number T32GM007388. This content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Notes The authors declare no competing financial interest.
Funding Information:
M.J.R also gratefully acknowledges support as a National Science Foundation (NSF) Graduate Research Fellow. M.J.R was also supported by the National Institute of General Medical Sciences (NIGMS) of the NIH under Grant Number T32GM007388. This content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2018/1/9
Y1 - 2018/1/9
N2 - Centrosomes are self-assembling, micron-scale, nonmembrane bound organelles that nucleate microtubules (MTs) and organize the microtubule cytoskeleton of the cell. They orchestrate critical cellular processes such as ciliary-based motility, vesicle trafficking, and cell division. Much is known about the role of the centrosome in these contexts, but we have a less comprehensive understanding of how the centrosome assembles and generates microtubules. Studies over the past 10 years have fundamentally shifted our view of these processes. Subdiffraction imaging has probed the amorphous haze of material surrounding the core of the centrosome revealing a complex, hierarchically organized structure whose composition and size changes profoundly during the transition from interphase to mitosis. New biophysical insights into protein phase transitions, where a diffuse protein spontaneously separates into a locally concentrated, nonmembrane bounded compartment, have provided a fresh perspective into how the centrosome might rapidly condense from diffuse cytoplasmic components. In this Perspective, we focus on recent findings that identify several centrosomal proteins that undergo phase transitions. We discuss how to reconcile these results with the current model of the underlying organization of proteins in the centrosome. Furthermore, we reflect on how these findings impact our understanding of how the centrosome undergoes self-assembly and promotes MT nucleation.
AB - Centrosomes are self-assembling, micron-scale, nonmembrane bound organelles that nucleate microtubules (MTs) and organize the microtubule cytoskeleton of the cell. They orchestrate critical cellular processes such as ciliary-based motility, vesicle trafficking, and cell division. Much is known about the role of the centrosome in these contexts, but we have a less comprehensive understanding of how the centrosome assembles and generates microtubules. Studies over the past 10 years have fundamentally shifted our view of these processes. Subdiffraction imaging has probed the amorphous haze of material surrounding the core of the centrosome revealing a complex, hierarchically organized structure whose composition and size changes profoundly during the transition from interphase to mitosis. New biophysical insights into protein phase transitions, where a diffuse protein spontaneously separates into a locally concentrated, nonmembrane bounded compartment, have provided a fresh perspective into how the centrosome might rapidly condense from diffuse cytoplasmic components. In this Perspective, we focus on recent findings that identify several centrosomal proteins that undergo phase transitions. We discuss how to reconcile these results with the current model of the underlying organization of proteins in the centrosome. Furthermore, we reflect on how these findings impact our understanding of how the centrosome undergoes self-assembly and promotes MT nucleation.
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U2 - 10.1021/acs.biochem.7b01064
DO - 10.1021/acs.biochem.7b01064
M3 - Review article
C2 - 29256606
AN - SCOPUS:85040308566
SN - 0006-2960
VL - 57
SP - 30
EP - 37
JO - Biochemistry
JF - Biochemistry
IS - 1
ER -