bims-nucpor 2022-04-03 papers

on Nuclear pore complex and nucleoporins in stress, aging and disease

Issue of 2022–04–03
two papers selected by
Sara Mingu, Johannes Gutenberg University

Quantitative analysis of nuclear pore complex organization in Schizosaccharomyces pombe.
Exportin 1 modulates life span by regulating nucleolar dynamics via the autophagy protein LGG-1/GABARAP.

Life Sci Alliance. 2022 Jul;pii: e202201423. [Epub ahead of print]5(7):

Quantitative analysis of nuclear pore complex organization in Schizosaccharomyces pombe.

Joseph M Varberg, Jay R Unruh, Andrew J Bestul, Azqa A Khan, Sue L Jaspersen.

The number, distribution, and composition of nuclear pore complexes (NPCs) in the nuclear envelope varies between cell types and changes during cellular differentiation and in disease. To understand how NPC density and organization are controlled, we analyzed the NPC number and distribution in the fission yeast Schizosaccharomyces pombe using structured illumination microscopy. The small size of yeast nuclei, genetic features of fungi, and our robust image analysis pipeline allowed us to study NPCs in intact nuclei under multiple conditions. Our data revealed that NPC density is maintained across a wide range of nuclear sizes. Regions of reduced NPC density are observed over the nucleolus and surrounding the spindle pole body (SPB). Lem2-mediated tethering of the centromeres to the SPB is required to maintain NPC exclusion near SPBs. These findings provide a quantitative understanding of NPC number and distribution in S. pombe and show that interactions between the centromere and the nuclear envelope influences local NPC distribution.

DOI: https://doi.org/10.26508/lsa.202201423
Sci Adv. 2022 Apr;8(13): eabj1604

Exportin 1 modulates life span by regulating nucleolar dynamics via the autophagy protein LGG-1/GABARAP.

Anita V Kumar, Taewook Kang, Tara G Thakurta, Celeste Ng, Aric N Rogers, Martin R Larsen, Louis R Lapierre.

Altered nucleolar and ribosomal dynamics are key hallmarks of aging, but their regulation remains unclear. Building on the knowledge that the conserved nuclear export receptor Exportin 1 (XPO-1/XPO1) modulates proteostasis and life span, we systematically analyzed the impact of nuclear export on protein metabolism. Using transcriptomic and subcellular proteomic analyses in nematodes, we demonstrate that XPO-1 modulates the nucleocytoplasmic distribution of key proteins involved in nucleolar dynamics and ribosome function, including fibrillarin (FIB-1/FBL) and RPL-11 (RPL11). Silencing xpo-1 led to marked reduction in global translation, which was accompanied by decreased nucleolar size and lower fibrillarin levels. A targeted screen of known proteostatic mediators revealed that the autophagy protein LGG-1/GABARAP modulates nucleolar size by regulating RPL-11 levels, linking specific protein degradation to ribosome metabolism. Together, our study reveals that nucleolar size and life span are regulated by LGG-1/GABARAP via ribosome protein surveillance.

DOI: https://doi.org/10.1126/sciadv.abj1604