A hub-and-spoke nuclear lamina architecture in trypanosomes.

Martin Zoltner,Ludek Koreny,Julius Lukeš,Marie Vancová,Jennifer Holden,Norma E Padilla-Mejia,Mark C Field

doi:10.1242/jcs.251264

Abstract

ABSTRACTThe nuclear lamina supports many functions, including maintaining nuclear structure and gene expression control, and correct spatio-temporal assembly is vital to meet these activities. Recently, multiple lamina systems have been described that, despite independent evolutionary origins, share analogous functions. In trypanosomatids the two known lamina proteins, NUP-1 and NUP-2, have molecular masses of 450 and 170 kDa, respectively, which demands a distinct architecture from the ∼60 kDa lamin-based system of metazoa and other lineages. To uncover organizational principles for the trypanosome lamina we generated NUP-1 deletion mutants to identify domains and their arrangements responsible for oligomerization. We found that both the N- and C-termini act as interaction hubs, and that perturbation of these interactions impacts additional components of the lamina and nuclear envelope. Furthermore, the assembly of NUP-1 terminal domains suggests intrinsic organizational capacity. Remarkably, there is little impact on silencing of telomeric variant surface glycoprotein genes. We suggest that both terminal domains of NUP-1 have roles in assembling the trypanosome lamina and propose a novel architecture based on a hub-and-spoke configuration.

Highlights

The nucleus is delineated by a double lipid membrane bilayer, the nuclear envelope (NE) and supported by a proteinaceous lamina that influences nuclear shape, size and resilience to physical forces together with mechano-signaling capability (Gruenbam and Foisner, 2015; Swift and Discher, 2014)
In African trypanosomes the cell cycle can be assessed from the number and position of the nuclei and kinetoplasts
2K1N cells bearing extra structures containing chromatin are prevalent among these abnormal cells. These results indicate that TbNup98, apart from its function as part of the nuclear pore complex (NPC), it has an influence on mitosis, cytokinesis and/or normal segregation of chromatin and participates with

Summary

Introduction

The nucleus is delineated by a double lipid membrane bilayer, the nuclear envelope (NE) and supported by a proteinaceous lamina that influences nuclear shape, size and resilience to physical forces together with mechano-signaling capability (Gruenbam and Foisner, 2015; Swift and Discher, 2014). The lamina interacts with the nuclear pore complex (NPC), influencing position, function, organization and modification of chromatin (Aaronson et al, 1975; Goldberg et al, 1996; Liu et al, 2000). Lamins form homotypic filaments distributed throughout the nucleus with the separate networks interacting in a complex manner (Goldberg et al, 2008; Shimi et al, 2008, 2015; Turgay et al, 2017; Nmezi et al, 2019). Lamin B is highly ordered into layers and related to stabilization of nuclear shape, whilst lamin A forms bundles and is more associated with mechanical rigidity (Turgay et al, 2017; Nmezi et al, 2019)

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