Cell Reports (Sep 2021)
The prolyl-isomerase PIN1 is essential for nuclear Lamin-B structure and function and protects heterochromatin under mechanical stress
- Francesco Napoletano,
- Gloria Ferrari Bravo,
- Ilaria Anna Pia Voto,
- Aurora Santin,
- Lucia Celora,
- Elena Campaner,
- Clara Dezi,
- Arianna Bertossi,
- Elena Valentino,
- Mariangela Santorsola,
- Alessandra Rustighi,
- Valentina Fajner,
- Elena Maspero,
- Federico Ansaloni,
- Valeria Cancila,
- Cesare Fabio Valenti,
- Manuela Santo,
- Osvaldo Basilio Artimagnella,
- Sara Finaurini,
- Ubaldo Gioia,
- Simona Polo,
- Remo Sanges,
- Claudio Tripodo,
- Antonello Mallamaci,
- Stefano Gustincich,
- Fabrizio d’Adda di Fagagna,
- Fiamma Mantovani,
- Valeria Specchia,
- Giannino Del Sal
Affiliations
- Francesco Napoletano
- Laboratorio Nazionale CIB (LNCIB), Area Science Park, Padriciano 99, 34149 Trieste, Italy; Department of Life Sciences (DSV), University of Trieste, 34127 Trieste, Italy; Corresponding author
- Gloria Ferrari Bravo
- Laboratorio Nazionale CIB (LNCIB), Area Science Park, Padriciano 99, 34149 Trieste, Italy; Department of Life Sciences (DSV), University of Trieste, 34127 Trieste, Italy
- Ilaria Anna Pia Voto
- Laboratorio Nazionale CIB (LNCIB), Area Science Park, Padriciano 99, 34149 Trieste, Italy
- Aurora Santin
- Laboratorio Nazionale CIB (LNCIB), Area Science Park, Padriciano 99, 34149 Trieste, Italy
- Lucia Celora
- Laboratorio Nazionale CIB (LNCIB), Area Science Park, Padriciano 99, 34149 Trieste, Italy
- Elena Campaner
- Laboratorio Nazionale CIB (LNCIB), Area Science Park, Padriciano 99, 34149 Trieste, Italy; Department of Life Sciences (DSV), University of Trieste, 34127 Trieste, Italy
- Clara Dezi
- Department of Life Sciences (DSV), University of Trieste, 34127 Trieste, Italy
- Arianna Bertossi
- Laboratorio Nazionale CIB (LNCIB), Area Science Park, Padriciano 99, 34149 Trieste, Italy; Department of Life Sciences (DSV), University of Trieste, 34127 Trieste, Italy
- Elena Valentino
- Laboratorio Nazionale CIB (LNCIB), Area Science Park, Padriciano 99, 34149 Trieste, Italy
- Mariangela Santorsola
- Laboratorio Nazionale CIB (LNCIB), Area Science Park, Padriciano 99, 34149 Trieste, Italy; Department of Life Sciences (DSV), University of Trieste, 34127 Trieste, Italy
- Alessandra Rustighi
- Laboratorio Nazionale CIB (LNCIB), Area Science Park, Padriciano 99, 34149 Trieste, Italy; Department of Life Sciences (DSV), University of Trieste, 34127 Trieste, Italy
- Valentina Fajner
- FIRC Institute of Molecular Oncology (IFOM), 20139 Milan, Italy
- Elena Maspero
- FIRC Institute of Molecular Oncology (IFOM), 20139 Milan, Italy
- Federico Ansaloni
- Area of Neuroscience, International School for Advanced Studies (SISSA), 34146 Trieste, Italy
- Valeria Cancila
- Tumor Immunology Unit, Department of Health Science, Human Pathology Section, School of Medicine, University of Palermo, 90133 Palermo, Italy
- Cesare Fabio Valenti
- Tumor Immunology Unit, Department of Health Science, Human Pathology Section, School of Medicine, University of Palermo, 90133 Palermo, Italy
- Manuela Santo
- Area of Neuroscience, International School for Advanced Studies (SISSA), 34146 Trieste, Italy
- Osvaldo Basilio Artimagnella
- Area of Neuroscience, International School for Advanced Studies (SISSA), 34146 Trieste, Italy
- Sara Finaurini
- Area of Neuroscience, International School for Advanced Studies (SISSA), 34146 Trieste, Italy
- Ubaldo Gioia
- FIRC Institute of Molecular Oncology (IFOM), 20139 Milan, Italy
- Simona Polo
- FIRC Institute of Molecular Oncology (IFOM), 20139 Milan, Italy
- Remo Sanges
- Area of Neuroscience, International School for Advanced Studies (SISSA), 34146 Trieste, Italy
- Claudio Tripodo
- FIRC Institute of Molecular Oncology (IFOM), 20139 Milan, Italy; Tumor Immunology Unit, Department of Health Science, Human Pathology Section, School of Medicine, University of Palermo, 90133 Palermo, Italy
- Antonello Mallamaci
- Area of Neuroscience, International School for Advanced Studies (SISSA), 34146 Trieste, Italy
- Stefano Gustincich
- Area of Neuroscience, International School for Advanced Studies (SISSA), 34146 Trieste, Italy; Central RNA Laboratory, Italian Institute of Technology, 16163 Genova, Italy
- Fabrizio d’Adda di Fagagna
- FIRC Institute of Molecular Oncology (IFOM), 20139 Milan, Italy; Institute of Molecular Genetics, National Research Institute (CNR), Pavia, Italy
- Fiamma Mantovani
- Laboratorio Nazionale CIB (LNCIB), Area Science Park, Padriciano 99, 34149 Trieste, Italy; Department of Life Sciences (DSV), University of Trieste, 34127 Trieste, Italy
- Valeria Specchia
- Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, 73100 Lecce, Italy
- Giannino Del Sal
- Laboratorio Nazionale CIB (LNCIB), Area Science Park, Padriciano 99, 34149 Trieste, Italy; Department of Life Sciences (DSV), University of Trieste, 34127 Trieste, Italy; FIRC Institute of Molecular Oncology (IFOM), 20139 Milan, Italy; Corresponding author
- Journal volume & issue
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Vol. 36,
no. 11
p. 109694
Abstract
Summary: Chromatin organization plays a crucial role in tissue homeostasis. Heterochromatin relaxation and consequent unscheduled mobilization of transposable elements (TEs) are emerging as key contributors of aging and aging-related pathologies, including Alzheimer’s disease (AD) and cancer. However, the mechanisms governing heterochromatin maintenance or its relaxation in pathological conditions remain poorly understood. Here we show that PIN1, the only phosphorylation-specific cis/trans prolyl isomerase, whose loss is associated with premature aging and AD, is essential to preserve heterochromatin. We demonstrate that this PIN1 function is conserved from Drosophila to humans and prevents TE mobilization-dependent neurodegeneration and cognitive defects. Mechanistically, PIN1 maintains nuclear type-B Lamin structure and anchoring function for heterochromatin protein 1α (HP1α). This mechanism prevents nuclear envelope alterations and heterochromatin relaxation under mechanical stress, which is a key contributor to aging-related pathologies.
