TY - JOUR
T1 - Aberrant Compartment Formation by HSPB2 Mislocalizes Lamin A and Compromises Nuclear Integrity and Function
AU - Morelli, Federica F
AU - Verbeek, Dineke S
AU - Bertacchini, Jessika
AU - Vinet, Jonathan
AU - Mediani, Laura
AU - Marmiroli, Sandra
AU - Cenacchi, Giovanna
AU - Nasi, Milena
AU - De Biasi, Sara
AU - Brunsting, Jeanette F
AU - Lammerding, Jan
AU - Pegoraro, Elena
AU - Angelini, Corrado
AU - Tupler, Rossella
AU - Alberti, Simon
AU - Carra, Serena
N1 - Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2017/8/29
Y1 - 2017/8/29
N2 - Small heat shock proteins (HSPBs) contain intrinsically disordered regions (IDRs), but the functions of these IDRs are still unknown. Here, we report that, in mammalian cells, HSPB2 phase separates to form nuclear compartments with liquid-like properties. We show that phase separation requires the disordered C-terminal domain of HSPB2. We further demonstrate that, in differentiating myoblasts, nuclear HSPB2 compartments sequester lamin A. Increasing the nuclear concentration of HSPB2 causes the formation of aberrant nuclear compartments that mislocalize lamin A and chromatin, with detrimental consequences for nuclear function and integrity. Importantly, phase separation of HSPB2 is regulated by HSPB3, but this ability is lost in two identified HSPB3 mutants that are associated with myopathy. Our results suggest that HSPB2 phase separation is involved in reorganizing the nucleoplasm during myoblast differentiation. Furthermore, these findings support the idea that aberrant HSPB2 phase separation, due to HSPB3 loss-of-function mutations, contributes to myopathy.
AB - Small heat shock proteins (HSPBs) contain intrinsically disordered regions (IDRs), but the functions of these IDRs are still unknown. Here, we report that, in mammalian cells, HSPB2 phase separates to form nuclear compartments with liquid-like properties. We show that phase separation requires the disordered C-terminal domain of HSPB2. We further demonstrate that, in differentiating myoblasts, nuclear HSPB2 compartments sequester lamin A. Increasing the nuclear concentration of HSPB2 causes the formation of aberrant nuclear compartments that mislocalize lamin A and chromatin, with detrimental consequences for nuclear function and integrity. Importantly, phase separation of HSPB2 is regulated by HSPB3, but this ability is lost in two identified HSPB3 mutants that are associated with myopathy. Our results suggest that HSPB2 phase separation is involved in reorganizing the nucleoplasm during myoblast differentiation. Furthermore, these findings support the idea that aberrant HSPB2 phase separation, due to HSPB3 loss-of-function mutations, contributes to myopathy.
U2 - 10.1016/j.celrep.2017.08.018
DO - 10.1016/j.celrep.2017.08.018
M3 - Article
C2 - 28854361
VL - 20
SP - 2100
EP - 2115
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 9
ER -