Genetic mutations strengthen functional association of LAP1 with DYT1 dystonia and muscular dystrophy

Rebelo, Sandra; Silva, Edgar F. da Cruz e

doi:10.1016/j.mrrev.2015.07.004

Cited by 22 publications

(20 citation statements)

References 60 publications

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“…This expression pattern shifts to the centriolar pole during elongation, before LAP1 perinuclear staining becomes poorly detectable in fully-mature spermatids, which are then released from the seminiferous epithelium into the tubular lumen. Despite being previously associated with cell cycle progression, NE integrity, DYT1 dystonia and skeletal muscle maintenance [14,15,16,45], LAP1 functional characterization is still not fully elucidated. Interestingly, it was not possible to verify the expected presence of LAP1 during meiosis, and rather surprisingly, LAP1 staining was mainly detected throughout mouse spermiogenesis (Figure 1 and Table 1).…”

Section: Discussionmentioning

confidence: 99%

“…However, despite being one of the first LAPs identified [13], the physiological functions of this ubiquitously-expressed NE protein remain poorly understood. Nevertheless, LAP1 has been implicated in the regulation of the NE structure, cell cycle progression, mitosis, NE localization of torsinA and regulation of its ATPase activity, as well as skeletal muscle maintenance [14,15,16]. In our previous work, LAP1 was found in the mitotic spindle, mid-body and centrosomes, indicating a strong functional association between LAP1 and these cell cycle-related components.…”

Section: Introductionmentioning

confidence: 99%

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Descriptive Analysis of LAP1 Distribution and That of Associated Proteins throughout Spermatogenesis

et al. 2017

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Spermatogenesis comprises highly complex differentiation processes. Nuclear envelope (NE) proteins have been associated with these processes, including lamins, lamina-associated polypeptide (LAP) 2 and the lamin B-receptor. LAP1 is an important NE protein whose function has not been fully elucidated, but several binding partners allow predicting putative LAP1 functions. To date, LAP1 had not been associated with spermatogenesis. In this study, LAP1 expression and cellular/subcellular localization during spermatogenesis in human and mouse testes is established for the first time. The fact that LAP1 is expressed during nuclear elongation in spermiogenesis and is located at the spermatids’ centriolar pole is singularly important. LAP1 binds to members of the protein phosphatase 1 (PP1) family. Similar localization of LAP1 and PP1γ2, a testis-specific PP1 isoform, suggests a shared function for both proteins during spermiogenesis. Furthermore, this study suggests an involvement of LAP1 in manchette development and chromatin regulation possibly via interaction with acetylated α-tubulin and lamins, respectively. Taken together, the present results indicate that, by moving to the posterior pole in spermatids, LAP1 can contribute to the achievement of non-random, sperm-specific chromatin distribution, as well as modulate cellular remodeling during spermiogenesis. In addition, LAP1 seems to be associated with dynamic microtubule changes related to manchette formation and flagella development.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Descriptive Analysis of LAP1 Distribution and That of Associated Proteins throughout Spermatogenesis

et al. 2017

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“…LAP1 is structurally composed of a nucleoplasmic N‐terminal domain that binds to A‐ and B‐type lamins, emerin and protein phosphatase 1 (PP1), followed by a single transmembrane segment and a perinuclear C‐terminal domain that interacts with torsinA (Rebelo, da Cruz e Silva & da Cruz e Silva, ; Shin, Dauer & Worman, ). The precise physiological role of LAP1 is not completely elucidated, although some functions have been suggested based on its association with several proteins at the NE in somatic cells, namely positioning of lamins and chromatin at the nuclear periphery, activation of torsinA ATPase activity, regulation of the localization of emerin:A‐type lamin complexes at the INM (Rebelo et al ., ), maintenance of NE structure and cell cycle progression (Santos et al ., ). Recently, a putative involvement of LAP1 in spermiogenesis‐specific nuclear remodelling has also been proposed (Table ; see Section III.2) (Serrano et al ., ).…”

Section: Nuclear Envelope Proteins Relevant To Mammalian Spermatogenesismentioning

confidence: 99%

Nuclear envelope dynamics during mammalian spermatogenesis: new insights on male fertility

et al. 2019

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The production of highly specialized spermatozoa from undifferentiated spermatogonia is a strictly organized and programmed process requiring extensive restructuring of the entire cell. One of the most remarkable cellular transformations accompanying the various phases of spermatogenesis is the profound remodelling of the nuclear architecture, in which the nuclear envelope (NE) seems to be crucially involved. In recent years, several proteins from the distinct layers forming the NE (i.e. the inner and outer nuclear membranes as well as the nuclear lamina) have been associated with meiosis and/or spermiogenesis in different mammalian species. Among these are A-and B-type lamins, Dpy-19-like protein 2 (DPY19L2), lamin B receptor (LBR), lamina-associated polypeptide 1 (LAP1), LAP2/emerin/MAN1 (LEM) domain-containing proteins, spermatogenesis-associated 46 (SPATA46) and diverse elements of the linker of nucleoskeleton and cytoskeleton (LINC) complex, namely Sad-1/UNC-84 homology (SUN) and Klarsicht/ANC-1/Syne-1 homology (KASH) domain-containing proteins. Herein, we summarize the current state of the art on the cellular and subcellular distribution of NE proteins expressed during mammalian spermatogenesis, and discuss the latest research developments regarding their testis-specific functions. This review provides a comprehensive and innovative overview of the NE network as a regulatory platform and as an essential determinant of efficient meiotic chromosome recombination as well as spermiogenesis-associated nuclear remodelling and differentiation in mammalian male germline cells. Thus, this review provides important novel insights on the biological relevance of NE proteins for male fertility.

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“…Initially discovered in rat liver nuclear envelope extracts (Senior and Gerace 1988 ), they have recently been described in mouse cardiac and skeletal muscle (Shin et al 2014 , 2013 ). LAP1B and LAP1C are expressed in human hearts, with LAP1B thought to be the predominant isoform (Rebelo et al 2015 ; Santos et al 2014 ).…”

Section: Lamina-associated Polypeptidementioning

confidence: 99%

Linker of nucleoskeleton and cytoskeleton complex proteins in cardiomyopathy

Stroud

2018

Biophys Rev

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The linker of nucleoskeleton and cytoskeleton (LINC) complex couples the nuclear lamina to the cytoskeleton. The LINC complex and its associated proteins play diverse roles in cells, ranging from genome organization, nuclear morphology, gene expression, to mechanical stability. The importance of a functional LINC complex is highlighted by the large number of mutations in genes encoding LINC complex proteins that lead to skeletal and cardiac myopathies. In this review, the structure, function, and interactions between components of the LINC complex will be described. Mutations that are known to cause cardiomyopathy in patients will be discussed alongside their respective mouse models. Furthermore, future challenges for the field and emerging technologies to investigate LINC complex function will be discussed.

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Genetic mutations strengthen functional association of LAP1 with DYT1 dystonia and muscular dystrophy

Cited by 22 publications

References 60 publications

Descriptive Analysis of LAP1 Distribution and That of Associated Proteins throughout Spermatogenesis

Descriptive Analysis of LAP1 Distribution and That of Associated Proteins throughout Spermatogenesis

Nuclear envelope dynamics during mammalian spermatogenesis: new insights on male fertility

Linker of nucleoskeleton and cytoskeleton complex proteins in cardiomyopathy

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