Cell Biology

LAP2alpha maintains a mobile and low assembly state of A-type lamins in the nuclear interior

1. Nana Naetar
2. Konstantina Georgiou
3. Christian Knapp
4. Irena Bronshtein
5. Elisabeth Zier
6. Petra Fichtinger
7. Thomas Dechat
8. Yuval Garini
9. Roland Foisner

• Curated by eLife

  Summary: This work builds on prior studies by the Foisner group that investigated the function(s) of the soluble A-type lamin binding protein, LAP2a. One of their prior observations using antibody labeling was that there appeared to be a depletion of the nucleoplasmic pool of A-type lamins in cells lacking LAP2a. In this manuscript, the authors employ CRISPR-Cas9 editing to develop new tools to investigate the attributes specific to nucleoplasmic versus lamina-integrated A-type lamins. Using this new approach (and comparing it with their prior observations), the authors hit upon a new model in which LAP2a influences the conformational state of A-type lamins, which in turn influences its detection by a commonly used antibody. This technical detail explains the new realization that nucleoplasmic lamin A persists in LAP2a-null cells, albeit in a different state. The authors provide evidence that LAP2a antagonizes stable lamin A filament assembly, that is absence leads to stabilized intranuclear lamin A assemblies, and that telomere mobility is negatively influenced by loss of LAP2a in a manner depending on the presence of lamin A/C. The authors' work further identifies two pathways by which nucleoplasmic lamins emerge, namely by 1) initial localization to the lamina followed by relocalization to the nucleoplasm, and 2) from the pool of mitotic lamins which are not associated to the lamina.

  Overall there was enthusiasm for the study, with the reviewers stating their appreciation for the author's mechanistic approach to studying lamin assembly state and the use of complementary cell biology/microscopy and biochemical approaches. The rigor of the science was also lauded, including inclusion of, for example, genome editing quality control measures. Taken together the reviewers felt that the findings provided a new perspective on how LAP2a influences the state of A-type lamins. As the impact of lamins on nuclear organization is critical for nuclear functions and important for nuclear integrity, these results are fundamental for the understanding of both lamin A/C and LAP2a.

Reviewed by eLife

The multi‐scale architecture of mammalian sperm flagella and implications for ciliary motility

1. Miguel Ricardo Leung
2. Marc C Roelofs
3. Ravi Teja Ravi
4. Paula Maitan
5. Heiko Henning
6. Min Zhang
7. Elizabeth G Bromfield
8. Stuart C Howes
9. Bart M Gadella
10. Hermes Bloomfield‐Gadêlha
11. Tzviya Zeev‐Ben‐Mordehai

Reviewed by Review Commons

Septins coordinate cell wall integrity and lipid metabolism in a sphingolipid-dependent process

1. Alexander Mela
2. Michelle Momany

Reviewed by Review Commons

Kinesin-4 KIF21B limits microtubule growth to allow rapid centrosome polarization in T cells

1. Peter Jan Hooikaas
2. Hugo GJ Damstra
3. Oane J Gros
4. Wilhelmina E van Riel
5. Maud Martin
6. Yesper TH Smits
7. Jorg van Loosdregt
8. Lukas C Kapitein
9. Florian Berger
10. Anna Akhmanova

• Curated by eLife

  Summary: This is a very interesting study addressing the question of microtubule cytoskeleton reorganization in the immunological synapse. Specifically, the work demonstrates the contribution of KIF21B for the control of the T cell microtubule (MT) network required for T cell polarization during immunological synapse formation. The authors use a variety of microscopy techniques, including expansion microscopy, controlled perturbations of the cell, and computer simulations to generate their results. The authors show that knockout of KIF21B results in longer MTs that result in an inability to polarise the MT network by a mechanism consistent with dynein motor function at the immunological synapse to capture long MTs and center the MT aster at the synapse. They use the Jurkat cell line, which is a classical model for this step in immune synapse function and fully appropriate. They show that KIF21B-GFP can rescue the knockout phenotype and then use this as a way to follow KIF12B dynamics in the Jurkat cells. KIF21B works by inducing pausing and catastrophe, thus, more MTs are shorter when present. They also rescue the defect in the KIF21B KOs with 0.5 nM vinblastine, that directly increases catastrophes, shortens the MTs and restores MT network polarization to the synapse. As a functional surrogate they investigate lysosome positioning at the synapse, which is one of the proposed functions of this cytoskeletal polarization. The use of expansion microscopy in this system is relatively new and clearly very powerful. The modelling component adds to the story and supports the sliding model proposed by Poenie and colleagues in 2006, but cannot say that there is no component of end capture and shrinkage as proposed by Hammer and colleagues more recently. Experiments and modelling are performed to a high standard and the results advance the field.

Reviewed by eLife

The capacity of origins to load MCM establishes replication timing patterns

1. Livio Dukaj
2. Nicholas Rhind

Reviewed by Review Commons

Trim39 regulates neuronal apoptosis by acting as a SUMO-targeted E3 ubiquitin-ligase for the transcription factor NFATc3

1. Meenakshi Basu-Shrivastava
2. Barbara Mojsa
3. Stéphan Mora
4. Ian Robbins
5. Guillaume Bossis
6. Iréna Lassot
7. Solange Desagher

Reviewed by Review Commons

A polarity pathway for exocyst-dependent intracellular tube extension

1. Joshua Abrams
2. Jeremy Nance

Reviewed by Review Commons

Membrane binding controls ordered self-assembly of animal septins

1. Agata Szuba
2. Fouzia Bano
3. Gerard Castro-Linares
4. Francois Iv
5. Manos Mavrakis
6. Ralf P Richter
7. Aurélie Bertin
8. Gijsje H Koenderink

Reviewed by eLife

Osmolarity-independent electrical cues guide rapid response to injury in zebrafish epidermis

1. Andrew S Kennard
2. Julie A Theriot

Reviewed by eLife, preLights

EFF-1 promotes muscle fusion, paralysis and retargets infection by AFF-1-coated viruses in C. elegans

1. Anna Meledin
2. Xiaohui Li
3. Elena Matveev
4. Boaz Gildor
5. Ofer Katzir
6. Benjamin Podbilewicz

Reviewed by eLife