scholarly journals Coupling of the nucleus and cytoplasm: Role of the LINC complex

2005 ◽  
Vol 172 (1) ◽  
pp. 41-53 ◽  
Author(s):  
Melissa Crisp ◽  
Qian Liu ◽  
Kyle Roux ◽  
J.B. Rattner ◽  
Catherine Shanahan ◽  
...  
Keyword(s):  
Nuclear Membrane ◽  
Integral Membrane Proteins ◽  
Actin Binding ◽  
Linc Complex ◽  
Outer Membranes ◽  
Perinuclear Space ◽  
Actin Binding Domain ◽  
Lumenal Domain ◽  
Integral Proteins

The nuclear envelope defines the barrier between the nucleus and cytoplasm and features inner and outer membranes separated by a perinuclear space (PNS). The inner nuclear membrane contains specific integral proteins that include Sun1 and Sun2. Although the outer nuclear membrane (ONM) is continuous with the endoplasmic reticulum, it is nevertheless enriched in several integral membrane proteins, including nesprin 2 Giant (nesp2G), an 800-kD protein featuring an NH2-terminal actin-binding domain. A recent study (Padmakumar, V.C., T. Libotte, W. Lu, H. Zaim, S. Abraham, A.A. Noegel, J. Gotzmann, R. Foisner, and I. Karakesisoglou. 2005. J. Cell Sci. 118:3419–3430) has shown that localization of nesp2G to the ONM is dependent upon an interaction with Sun1. In this study, we confirm and extend these results by demonstrating that both Sun1 and Sun2 contribute to nesp2G localization. Codepletion of both of these proteins in HeLa cells leads to the loss of ONM-associated nesp2G, as does overexpression of the Sun1 lumenal domain. Both treatments result in the expansion of the PNS. These data, together with those of Padmakumar et al. (2005), support a model in which Sun proteins tether nesprins in the ONM via interactions spanning the PNS. In this way, Sun proteins and nesprins form a complex that links the nucleoskeleton and cytoskeleton (the LINC complex).

scholarly journals The WASP Homologue Las17 Activates the Novel Actin-regulatory Activity of Ysc84 to Promote Endocytosis in Yeast

2009 ◽  
Vol 20 (6) ◽  
pp. 1618-1628 ◽  
Author(s):  
Alastair S. Robertson ◽  
Ellen G. Allwood ◽  
Adam P.C. Smith ◽  
Fiona C. Gardiner ◽  
Rosaria Costa ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
Actin Polymerization ◽  
Actin Binding ◽  
The Novel ◽  
Cellular Processes ◽  
New Class ◽  
Actin Binding Domain ◽  
Kinetics Of ◽  
Actin Binding Site

Actin plays an essential role in many eukaryotic cellular processes, including motility, generation of polarity, and membrane trafficking. Actin function in these roles is regulated by association with proteins that affect its polymerization state, dynamics, and organization. Numerous proteins have been shown to localize with cortical patches of yeast actin during endocytosis, but the role of many of these proteins remains poorly understood. Here, we reveal that the yeast protein Ysc84 represents a new class of actin-binding proteins, conserved from yeast to humans. It contains a novel N-terminal actin-binding domain termed Ysc84 actin binding (YAB), which can bind and bundle actin filaments. Intriguingly, full-length Ysc84 alone does not bind to actin, but binding can be activated by a specific motif within the polyproline region of the yeast WASP homologue Las17. We also identify a new monomeric actin-binding site on Las17. Together, the polyproline region of Las17 and Ysc84 can promote actin polymerization. Using live cell imaging, kinetics of assembly and disassembly of proteins at the endocytic site were analyzed and reveal that loss of Ysc84 and its homologue Lsb3 decrease inward movement of vesicles consistent with a role in actin polymerization during endocytosis.

scholarly journals Integral membrane proteins specific to the inner nuclear membrane and associated with the nuclear lamina.

1988 ◽  
Vol 107 (6) ◽  
pp. 2029-2036 ◽  
Author(s):  
A Senior ◽  
L Gerace
Keyword(s):  
Membrane Proteins ◽  
Nuclear Membrane ◽  
Immunofluorescence Microscopy ◽  
Nuclear Lamina ◽  
Integral Membrane Proteins ◽  
Inner Nuclear Membrane ◽  
Attachment Sites ◽  
Nonionic Detergent ◽  
Pore Complexes ◽  
Integral Proteins

We obtained a monoclonal antibody (RL13) that identifies three integral membrane proteins specific to the nuclear envelope of rat liver, a major 75-kD polypeptide and two more minor components of 68 and 55 kD. Immunogold labeling of isolated nuclear envelopes demonstrates that these antigens are localized specifically to the inner nuclear membrane, and that the RL13 epitope occurs on the inner membrane's nucleoplasmic surface where the nuclear lamina is found. When nuclear envelopes are extracted with solutions containing nonionic detergent and high salt to solubilize nuclear membranes and pore complexes, most of these integral proteins remain associated with the insoluble lamina. Since the polypeptides recognized by RL13 are relatively abundant, they may function as lamina attachment sites in the inner nuclear membrane. Major cross-reacting antigens are found by immunoblotting and immunofluorescence microscopy in all rat cells examined. Therefore, these integral proteins are biochemical markers for the inner nuclear membrane and will be useful models for studying nuclear membrane biogenesis.

scholarly journals The role of the nuclear envelope in the regulation of chromatin dynamics during cell division

2020 ◽  
Vol 71 (17) ◽  
pp. 5148-5159
Author(s):  
Nadia Fernández-Jiménez ◽  
Mónica Pradillo
Keyword(s):  
Cell Division ◽  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Recent Progress ◽  
Membrane System ◽  
Eukaryotic Cell ◽  
Chromatin Dynamics ◽  
Current State ◽  
Perinuclear Space

Abstract The nuclear envelope delineates the eukaryotic cell nucleus. The membrane system of the nuclear envelope consists of an outer nuclear membrane and an inner nuclear membrane separated by a perinuclear space. It serves as more than just a static barrier, since it regulates the communication between the nucleoplasm and the cytoplasm and provides the anchoring points where chromatin is attached. Fewer nuclear envelope proteins have been identified in plants in comparison with animals and yeasts. Here, we review the current state of knowledge of the nuclear envelope in plants, focusing on its role as a chromatin organizer and regulator of gene expression, as well as on the modifications that it undergoes to be efficiently disassembled and reassembled with each cell division. Advances in knowledge concerning the mitotic role of some nuclear envelope constituents are also presented. In addition, we summarize recent progress on the contribution of the nuclear envelope elements to telomere tethering and chromosome dynamics during the meiotic division in different plant species.

scholarly journals Role of Matrix and Fusion Proteins in Budding of Sendai Virus

2001 ◽  
Vol 75 (23) ◽  
pp. 11384-11391 ◽  
Author(s):  
Toru Takimoto ◽  
K. Gopal Murti ◽  
Tatiana Bousse ◽  
Ruth Ann Scroggs ◽  
Allen Portner
Keyword(s):  
Sendai Virus ◽  
Binding Domain ◽  
Site Directed Mutagenesis ◽  
M Protein ◽  
Actin Binding ◽  
Virus Like Particles ◽  
Actin Binding Domain ◽  
The Media ◽  
Human Parainfluenza Virus

ABSTRACT Paramyxoviruses are assembled at the surface of infected cells, where virions are formed by the process of budding. We investigated the roles of three Sendai virus (SV) membrane proteins in the production of virus-like particles. Expression of matrix (M) proteins from cDNA induced the budding and release of virus-like particles that contained M, as was previously observed with human parainfluenza virus type 1 (hPIV1). Expression of SV fusion (F) glycoprotein from cDNA caused the release of virus-like particles bearing surface F, although their release was less efficient than that of particles bearing M protein. Cells that expressed only hemagglutinin-neuraminidase (HN) released no HN-containing vesicles. Coexpression of M and F proteins enhanced the release of F protein by a factor greater than 4. The virus-like particles containing F and M were found in different density gradient fractions of the media of cells that coexpressed M and F, a finding that suggests that the two proteins formed separate vesicles and did not interact directly. Vesicles released by M or F proteins also contained cellular actin; therefore, actin may be involved in the budding process induced by viral M or F proteins. Deletion of C-terminal residues of M protein, which has a sequence similar to that of an actin-binding domain, significantly reduced release of the particles into medium. Site-directed mutagenesis of the cytoplasmic tail of F revealed two regions that affect the efficiency of budding: one domain comprising five consecutive amino acids conserved in SV and hPIV1 and one domain that is similar to the actin-binding domain required for budding induced by M protein. Our results indicate that both M and F proteins are able to drive the budding of SV and propose the possible role of actin in the budding process.

scholarly journals Accessorizing and anchoring the LINC complex for multifunctionality

2015 ◽  
Vol 208 (1) ◽  
pp. 11-22 ◽  
Author(s):  
Wakam Chang ◽  
Howard J. Worman ◽  
Gregg G. Gundersen
Keyword(s):  
Nuclear Membrane ◽  
Meiotic Chromosome ◽  
Linc Complex ◽  
Factors Associated ◽  
Ordered Arrays ◽  
Anchoring Proteins ◽  
Core Components ◽  
Chromosome Movements ◽  
Shed Light

The linker of nucleoskeleton and cytoskeleton (LINC) complex, composed of outer and inner nuclear membrane Klarsicht, ANC-1, and Syne homology (KASH) and Sad1 and UNC-84 (SUN) proteins, respectively, connects the nucleus to cytoskeletal filaments and performs diverse functions including nuclear positioning, mechanotransduction, and meiotic chromosome movements. Recent studies have shed light on the source of this diversity by identifying factors associated with the complex that endow specific functions as well as those that differentially anchor the complex within the nucleus. Additional diversity may be provided by accessory factors that reorganize the complex into higher-ordered arrays. As core components of the LINC complex are associated with several diseases, understanding the role of accessory and anchoring proteins could provide insights into pathogenic mechanisms.

scholarly journals Structure and Function of Filamin C in the Muscle Z-Disc

2020 ◽  
Vol 21 (8) ◽  
pp. 2696 ◽  
Author(s):  
Zhenfeng Mao ◽  
Fumihiko Nakamura
Keyword(s):  
Sequence Similarity ◽  
Actin Binding ◽  
Amino Acid Residues ◽  
Filamin A ◽  
Dimerization Domain ◽  
High Sequence Similarity ◽  
Actin Binding Domain ◽  
And Function ◽  
Filamin C

Filamin C (FLNC) is one of three filamin proteins (Filamin A (FLNA), Filamin B (FLNB), and FLNC) that cross-link actin filaments and interact with numerous binding partners. FLNC consists of a N-terminal actin-binding domain followed by 24 immunoglobulin-like repeats with two intervening calpain-sensitive hinges separating R15 and R16 (hinge 1) and R23 and R24 (hinge-2). The FLNC subunit is dimerized through R24 and calpain cleaves off the dimerization domain to regulate mobility of the FLNC subunit. FLNC is localized in the Z-disc due to the unique insertion of 82 amino acid residues in repeat 20 and necessary for normal Z-disc formation that connect sarcomeres. Since phosphorylation of FLNC by PKC diminishes the calpain sensitivity, assembly, and disassembly of the Z-disc may be regulated by phosphorylation of FLNC. Mutations of FLNC result in cardiomyopathy and muscle weakness. Although this review will focus on the current understanding of FLNC structure and functions in muscle, we will also discuss other filamins because they share high sequence similarity and are better characterized. We will also discuss a possible role of FLNC as a mechanosensor during muscle contraction.

scholarly journals Role of Binding of Plectin to the Integrin β4 Subunit in the Assembly of Hemidesmosomes

2004 ◽  
Vol 15 (3) ◽  
pp. 1211-1223 ◽  
Author(s):  
J. Koster ◽  
S. van Wilpe ◽  
I. Kuikman ◽  
S.H.M. Litjens ◽  
A. Sonnenberg
Keyword(s):  
Binding Sites ◽  
Cytoplasmic Domain ◽  
Actin Binding ◽  
Actin Binding Domain ◽  
Integrin Β4 ◽  
Fibronectin Type Iii ◽  
Intramolecular Association ◽  
Two Hybrid ◽  
Fibronectin Type

We have previously shown that plectin is recruited into hemidesmosomes through association of its actin-binding domain (ABD) with the first pair of fibronectin type III (FNIII) repeats and a small part of the connecting segment (residues 1328–1355) of the integrin β4 subunit. Here, we show that two proline residues (P1330 and P1333) in this region of the connecting segment are critical for supporting β4-mediated recruitment of plectin. Additional binding sites for the plakin domain of plectin on β4 were identified in biochemical and yeast two-hybrid assays. These sites are located at the end of the connecting segment (residues 1383–1436) and in the region containing the fourth FNIII repeat and the C-tail (residues 1570–1752). However, in cells, these additional binding sites cannot induce the assembly of hemidesmosomes without the interaction of the plectin-ABD with β4. Because the additional plectin binding sites overlap with sequences that mediate an intramolecular association of the β4 cytoplasmic domain, we propose that they are not accessible for binding and need to become exposed as the result of the binding of the plectin-ABD to β4. Furthermore, these additional binding sites might be necessary to position the β4 cytoplasmic domain for an optimal interaction with other hemidesmosomal components, thereby increasing the efficiency of hemidesmosome assembly.

scholarly journals Mena regulates the LINC complex to control actin–nuclear lamina associations, trans-nuclear membrane signalling and cancer gene expression

2021 ◽  
Author(s):  
Frederic Li Mow Chee ◽  
Bruno Beernaert ◽  
Alexander E P Loftus ◽  
Yatendra Kumar ◽  
Billie G C Griffith ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nuclear Envelope ◽  
Cancer Progression ◽  
Nuclear Membrane ◽  
Regulatory Protein ◽  
Nuclear Periphery ◽  
Nuclear Lamina ◽  
Actin Binding ◽  
Cancer Gene ◽  
Linc Complex

Interactions between cells and the extracellular matrix, mediated by integrin adhesion complexes (IACs), play key roles in cancer progression and metastasis. We investigated systems-level changes in the integrin adhesome during metastatic progression of a patient-derived cutaneous squamous cell carcinoma (cSCC), and found that the actin regulatory protein Mena is enriched in IACs in metastatic cSCC cells. Mena is connected within a subnetwork of actin-binding proteins to the LINC complex component nesprin-2, with which it interacts and co-localises at the nuclear envelope of metastatic cells. Moreover, Mena potentiates the interactions of nesprin-2 with the actin cytoskeleton and the nuclear lamina. CRISPR-mediated Mena depletion causes altered nuclear morphology, reduces tyrosine phosphorylation of the nuclear membrane protein emerin and downregulates expression of the immunomodulatory gene PTX3 via the recruitment of its enhancer to the nuclear periphery. We have uncovered an unexpected novel role for Mena at the nuclear membrane, where it controls the LINC complex, nuclear architecture, chromatin repositioning and cancer gene expression. This is the first description of an adhesion protein regulating gene transcription via direct signalling across the nuclear envelope.

Sign in / Sign up

Export Citation Format

Share Document