The Nuclear Lamina: Protein Accumulation and Disease
Carla Almendáriz-Palacios,
Zoe E. Gillespie,
Matthew Janzen,
Valeria Martinez,
Joanna M. Bridger,
Troy A. A. Harkness,
Darrell D. Mousseau,
Christopher H. Eskiw
Affiliations
Carla Almendáriz-Palacios
Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon, SK S7N 5A8, Canada
Zoe E. Gillespie
Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK S7N 5A8, Canada
Matthew Janzen
Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK S7N 5A8, Canada
Valeria Martinez
Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon, SK S7N 5A8, Canada
Joanna M. Bridger
Centre for Genome Engineering and Maintenance, College of Health, Life and Medical Sciences, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, UK
Troy A. A. Harkness
Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK S7N 5A8, Canada
Darrell D. Mousseau
Cell Signalling Laboratory, Department of Psychiatry, University of Saskatchewan, Saskatoon, SK S7N 5A5, Canada
Christopher H. Eskiw
Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon, SK S7N 5A8, Canada
Cellular health is reliant on proteostasis—the maintenance of protein levels regulated through multiple pathways modulating protein synthesis, degradation and clearance. Loss of proteostasis results in serious disease and is associated with aging. One proteinaceous structure underlying the nuclear envelope—the nuclear lamina—coordinates essential processes including DNA repair, genome organization and epigenetic and transcriptional regulation. Loss of proteostasis within the nuclear lamina results in the accumulation of proteins, disrupting these essential functions, either via direct interactions of protein aggregates within the lamina or by altering systems that maintain lamina structure. Here we discuss the links between proteostasis and disease of the nuclear lamina, as well as how manipulating specific proteostatic pathways involved in protein clearance could improve cellular health and prevent/reverse disease.
