scholarly journals Lamin B1 and lamin B2 are long-lived proteins with distinct functions in retinal development

2016 ◽  
Vol 27 (12) ◽  
pp. 1928-1937 ◽  
Author(s):  
David Razafsky ◽  
Candace Ward ◽  
Chloe Potter ◽  
Wanqiu Zhu ◽  
Yunlu Xue ◽  
...  
Keyword(s):  
Nuclear Lamina ◽  
Building Blocks ◽  
Postnatal Life ◽  
Cone Photoreceptors ◽  
Obvious Effect ◽  
Lamin B1 ◽  
Embryonic Neurogenesis ◽  
And Function ◽  
Embryonic Retina ◽  
Rod And Cone Photoreceptors

Lamin B1 and lamin B2 are essential building blocks of the nuclear lamina, a filamentous meshwork lining the nucleoplasmic side of the inner nuclear membrane. Deficiencies in lamin B1 and lamin B2 impair neurodevelopment, but distinct functions for the two proteins in the development and homeostasis of the CNS have been elusive. Here we show that embryonic depletion of lamin B1 in retinal progenitors and postmitotic neurons affects nuclear integrity, leads to the collapse of the laminB2 meshwork, impairs neuronal survival, and markedly reduces the cellularity of adult retinas. In stark contrast, a deficiency of lamin B2 in the embryonic retina has no obvious effect on lamin B1 localization or nuclear integrity in embryonic retinas, suggesting that lamin B1, but not lamin B2, is strictly required for nucleokinesis during embryonic neurogenesis. However, the absence of lamin B2 prevents proper lamination of adult retinal neurons, impairs synaptogenesis, and reduces cone photoreceptor survival. We also show that lamin B1 and lamin B2 are extremely long-lived proteins in rod and cone photoreceptors. OF interest, a complete absence of both proteins during postnatal life has little or no effect on the survival and function of cone photoreceptors.

scholarly journals Concentration-dependent lamin assembly and its roles in the localization of other nuclear proteins

2014 ◽  
Vol 25 (8) ◽  
pp. 1287-1297 ◽  
Author(s):  
Yuxuan Guo ◽  
Youngjo Kim ◽  
Takeshi Shimi ◽  
Robert D. Goldman ◽  
Yixian Zheng
Keyword(s):  
Nuclear Lamina ◽  
Nuclear Pore ◽  
Lamin A ◽  
Nuclear Pore Complexes ◽  
Developmental Defects ◽  
Protein Levels ◽  
Lamin B1 ◽  
Mouse Cells ◽  
Pore Complexes ◽  
And Function

The nuclear lamina (NL) consists of lamin polymers and proteins that bind to the polymers. Disruption of NL proteins such as lamin and emerin leads to developmental defects and human diseases. However, the expression of multiple lamins, including lamin-A/C, lamin-B1, and lamin-B2, in mammals has made it difficult to study the assembly and function of the NL. Consequently, it has been unclear whether different lamins depend on one another for proper NL assembly and which NL functions are shared by all lamins or are specific to one lamin. Using mouse cells deleted of all or different combinations of lamins, we demonstrate that the assembly of each lamin into the NL depends primarily on the lamin concentration present in the nucleus. When expressed at sufficiently high levels, each lamin alone can assemble into an evenly organized NL, which is in turn sufficient to ensure the even distribution of the nuclear pore complexes. By contrast, only lamin-A can ensure the localization of emerin within the NL. Thus, when investigating the role of the NL in development and disease, it is critical to determine the protein levels of relevant lamins and the intricate shared or specific lamin functions in the tissue of interest.

scholarly journals The versatility of Ascorbate Peroxidase-aided mapping uncovers insights of the nuclear lamina interactions and function

2020 ◽  
Author(s):  
Joseph R. Tran ◽  
Danielle I. Paulson ◽  
James J. Moresco ◽  
Stephen A. Adam ◽  
John R. Yates ◽  
...  
Keyword(s):  
Protein Trafficking ◽  
Nuclear Lamina ◽  
Sequence Motif ◽  
Proximity Ligation ◽  
Lamin B1 ◽  
Histone Lysine ◽  
And Function ◽  
Systematic Identification ◽  
Rna And Dna

AbstractThe nuclear lamina (NL) is a proteinaceous network found beneath the inner nuclear membrane. The NL is linked to a number of dynamic cellular activities including chromatin organization, transcription and RNA/protein trafficking through nuclear pores. Our understanding of the NL has been hindered in part by the general insolubility and low extractability of proteins from this region. This has spurred the development of proximity ligation methods that label proteins and/or DNA near the NL for systematic identification (Bar et al., 2018; Chen et al., 2018b; Guelen et al., 2008; Roux et al., 2012). To simplify labeling and improve temporal resolution, we fused APEX2 (Hung et al., 2014; Lam et al., 2015) to the nuclear lamina protein lamin-B1 to map proteins, RNA and DNA associated with the NL. We show that APEX2 labeling of the NL is robust and requires as little as 20 seconds. In addition to identifying the NL proteome, this method revealed NL-proximal RNA species that were largely spliced. These NL-proximal RNAs show a bias toward long 3’ UTRs, suggesting an RNA-regulatory role of the NL. This is further supported by the finding of a bias toward longer 3’ UTRs in genes deregulated in lamin-null cells. Interestingly, these RNAs share a sequence motif in their 3’ UTRs. Finally, we demonstrate that the APEX2 method can reliably map lamina-associated domains (LADs) at different stages of the cell cycle, revealing a variability of short LADs regions enriched for histone lysine 27 trimethylation (H3K27me3). Thus the APEX2 method report here is a useful addition to the molecular toolbox for the study of the NL and permits the identification of proteome, transcriptome, and genome elements associated with this nuclear substructure.

scholarly journals Lamin B1 acetylation slows the G1 to S cell cycle transition through inhibition of DNA repair

2021 ◽  
Author(s):  
Laura A Murray-Nerger ◽  
Joshua L Justice ◽  
Pranav Rekapalli ◽  
Josiah E Hutton ◽  
Ileana M Cristea
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Posttranslational Modifications ◽  
Cell Cycle Progression ◽  
Nuclear Periphery ◽  
Virus Production ◽  
Nuclear Lamina ◽  
Regulatory Function ◽  
Herpesvirus Type ◽  
Lamin B1

Abstract The integrity and regulation of the nuclear lamina is essential for nuclear organization and chromatin stability, with its dysregulation being linked to laminopathy diseases and cancer. Although numerous posttranslational modifications have been identified on lamins, few have been ascribed a regulatory function. Here, we establish that lamin B1 (LMNB1) acetylation at K134 is a molecular toggle that controls nuclear periphery stability, cell cycle progression, and DNA repair. LMNB1 acetylation prevents lamina disruption during herpesvirus type 1 (HSV-1) infection, thereby inhibiting virus production. We also demonstrate the broad impact of this site on laminar processes in uninfected cells. LMNB1 acetylation negatively regulates canonical nonhomologous end joining by impairing the recruitment of 53BP1 to damaged DNA. This defect causes a delay in DNA damage resolution and a persistent activation of the G1/S checkpoint. Altogether, we reveal LMNB1 acetylation as a mechanism for controlling DNA repair pathway choice and stabilizing the nuclear periphery.

Sex Steroids and Human Behavior: Implications for Developmental Psychopathology

CNS Spectrums ◽  
2001 ◽  
Vol 6 (1) ◽  
pp. 75-88 ◽  
Author(s):  
Gerianne M. Alexander ◽  
Bradley S. Peterson
Keyword(s):  
Sex Differences ◽  
Human Behavior ◽  
Sex Steroids ◽  
Developmental Psychopathology ◽  
Mammalian Species ◽  
Brain Structures ◽  
Postnatal Life ◽  
Brain Structure And Function ◽  
Atypical Development ◽  
And Function

AbstractIn a variety of mammalian species, prenatal androgens organize brain structures and functions that are later activated by steroid hormones in postnatal life. In humans, studies of individuals with typical and atypical development suggest that sex differences in reproductive and nonreproductive behavior derive in part from similar prenatal and postnatal steroid effects on brain development. This paper provides a summary of research investigating hormonal influences on human behavior and describes how sex differences in the prevalences and natural histories of developmental psychopathologies may be consistent with these steroid effects. An association between patterns of sexual differentiation and specific forms of psychopathology suggests novel avenues for assessing the effects of sex steroids on brain structure and function, which may in turn improve our understanding of typical and atypical development in women and men.

scholarly journals Bioelectrocatalytic hydrogels from electron-conducting metallopolypeptides coassembled with bifunctional enzymatic building blocks

2008 ◽  
Vol 105 (40) ◽  
pp. 15275-15280 ◽  
Author(s):  
Ian R. Wheeldon ◽  
Joshua W. Gallaway ◽  
Scott Calabrese Barton ◽  
Scott Banta
Keyword(s):  
Polyphenol Oxidase ◽  
Building Block ◽  
Leucine Zipper ◽  
Electrical Contact ◽  
Building Blocks ◽  
Coiled Coils ◽  
Biofuel Cell ◽  
Random Coil ◽  
Catalytic Current ◽  
And Function

Here, we present two bifunctional protein building blocks that coassemble to form a bioelectrocatalytic hydrogel that catalyzes the reduction of dioxygen to water. One building block, a metallopolypeptide based on a previously designed triblock polypeptide, is electron-conducting. A second building block is a chimera of artificial α-helical leucine zipper and random coil domains fused to a polyphenol oxidase, small laccase (SLAC). The metallopolypeptide has a helix–random-helix secondary structure and forms a hydrogel via tetrameric coiled coils. The helical and random domains are identical to those fused to the polyphenol oxidase. Electron-conducting functionality is derived from the divalent attachment of an osmium bis-bipyrdine complex to histidine residues within the peptide. Attachment of the osmium moiety is demonstrated by mass spectroscopy (MS-MALDI-TOF) and cyclic voltammetry. The structure and function of the α-helical domains are confirmed by circular dichroism spectroscopy and by rheological measurements. The metallopolypeptide shows the ability to make electrical contact to a solid-state electrode and to the redox centers of modified SLAC. Neat samples of the modified SLAC form hydrogels, indicating that the fused α-helical domain functions as a physical cross-linker. The fusion does not disrupt dimer formation, a necessity for catalytic activity. Mixtures of the two building blocks coassemble to form a continuous supramolecular hydrogel that, when polarized, generates a catalytic current in the presence of oxygen. The specific application of the system is a biofuel cell cathode, but this protein-engineering approach to advanced functional hydrogel design is general and broadly applicable to biocatalytic, biosensing, and tissue-engineering applications.

A Molecular Artisans Guide to Supramolecular Coordination Complexes and Metal Organic Frameworks

2015 ◽  
Vol 03 (01n02) ◽  
pp. 1540004 ◽  
Author(s):  
Xialu Wu ◽  
David J. Young ◽  
T. S. Andy Hor
Keyword(s):  
Chemical Reactivity ◽  
Metal Organic Frameworks ◽  
Building Blocks ◽  
Coordination Complexes ◽  
Large Molecules ◽  
Molecular Building Blocks ◽  
Supramolecular Coordination ◽  
Metal Organic ◽  
Molecular Synthesis ◽  
And Function

As molecular synthesis advances, we are beginning to learn control of not only the chemical reactivity (and function) of molecules, but also of their interactions with other molecules. It is this basic idea that has led to the current explosion of supramolecular science and engineering. Parallel to this development, chemists have been actively pursuing the design of very large molecules using basic molecular building blocks. Herein, we review the general development of supramolecular chemistry and particularly of two new branches: supramolecular coordination complexes (SCCs) and metal organic frameworks (MOFs). These two fields are discussed in detail with typical examples to illustrate what is now possible and what challenges lie ahead for tomorrow's molecular artisans.

A Dynamic Route to Structure and Function: Recent Advances in Imine-Based Organic Nanostructured Materials

2013 ◽  
Vol 66 (1) ◽  
pp. 9 ◽  
Author(s):  
Yi Liu ◽  
Zhan-Ting Li
Keyword(s):  
Self Assembly ◽  
Reaction System ◽  
Functional Materials ◽  
Building Blocks ◽  
The Self ◽  
Interlocked Molecules ◽  
Functional Aspects ◽  
Imine Bond ◽  
And Function ◽  
Dynamic Route

The chemistry of imine bond formation from simple aldehyde and amine precursors is among the most powerful dynamic covalent chemistries employed for the construction of discrete molecular objects and extended molecular frameworks. The reversible nature of the C=N bond confers error-checking and proof-reading capabilities in the self-assembly process within a multi-component reaction system. This review highlights recent progress in the self-assembly of complex organic molecular architectures that are enabled by dynamic imine chemistry, including molecular containers with defined geometry and size, mechanically interlocked molecules, and extended frameworks and polymers, from building blocks with preprogrammed steric and electronic information. The functional aspects associated with the nanometer-scale features not only place these dynamically constructed nanostructures at the frontier of materials sciences, but also bring unprecedented opportunities for the discovery of new functional materials.

Sign in / Sign up

Export Citation Format

Share Document