Novel localisation and possible function of LIN7 and IRSp53 in mitochondria of HeLa cells

Ferrari, Ilaria; Crespi, Alice; Fornasari, Diego; Pietrini, Grazia

doi:10.1016/j.ejcb.2016.05.001

Cited by 6 publications

(7 citation statements)

References 43 publications

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“…Versilac, which is a naturally occurring proteolytic product of versican, can be pro-apoptotic or pro-inflammatory in some biological contexts. BAIAP2 (IRSp53) is considered an important regulator of membrane and actin dynamics at actin-rich subcellular structures such as filopodia and lamellipodia, is believed to affect neurite initiation and neuronal branching, and has been proposed to also affect mitochondrial morphology (Chen et al, 2015;Ferrari et al, 2016). The protein is expressed most strongly in the brain.…”

Section: Discussionmentioning

confidence: 99%

BVVL/ FL: features caused by SLC52A3 mutations; WDFY4 and TNFSF13B may be novel causative genes

Khani

Shamshiri

Taheri

et al. 2021

Neurobiology of Aging

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Brown-Vialetto-Van Laere(BVVL) and Fazio-Londe(FL) are disorders with ALS-like features, usually with recessive inheritance. We aimed to identify causative mutations in ten probands. Neurological examinations, genetic analysis, audiometry, MRI, biochemical and immunological testings, and/or muscle histopathology were performed. Mutations in known causative gene SLC52A3 were found in seven probands. More importantly, only one mutated allele was observed in several patients, and variable expressivity and incomplete penetrance were clearly noted. Environmental insults may contribute to variable presentations. Putative causative mutations in other genes were identified in three probands. Two of the genes, WDFY4 and TNFSF13B, have immune related functions. Inflammatory responses were implicated in the patient with the WDFY4 mutation. Malfunction of the immune system and mitochondrial anomalies were shown in the patient with the TNFSF13B mutation. Prevalence of heterozygous SLC52A3 BVVL causative mutations and notable variability in expressivity of homozygous and heterozygous genotypes are being reported for the first time.Identification of WDFY4 and TNFSF13B as candidate causative genes supports conjectures on involvement of the immune system in BVVL and ALS.

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Section: Discussionmentioning

confidence: 99%

BVVL/ FL: features caused by SLC52A3 mutations; WDFY4 and TNFSF13B may be novel causative genes

Khani

Shamshiri

Taheri

et al. 2021

Neurobiology of Aging

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“…The IRSp53 protein contains multiple domains for protein–protein interactions, including a PDZ domain-binding motif at its C-terminus for interaction with the scaffold protein LIN7 (also named MALS/Velis), and LIN7 association is required to positively regulate IRSp53 activity at specific membrane sites in epithelial and neuronal cells [14–17]. We therefore tested whether IRSp53 and LIN7 play a role in SOD1-dependent formation of lamellipodia by analysing the percentage of lamellipodia-bearing cells in SOD1 overexpressing N2A cells downregulated for/coexpressing IRSp53 or LIN7 (Figure 1(C–D)).…”

Section: Resultsmentioning

confidence: 99%

SOD1 stimulates lamellipodial protrusions in Neuro 2A cell lines

Ferrari

Verpelli

Crespi

et al. 2018

Communicative & Integrative Biology

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We here investigated the effects of overexpressed superoxide dismutase (SOD)1 and amyotrophic lateral sclerosis (ALS)-linked SOD1 mutants G93A and G147S in Neuro 2A (N2A) cell lines, and found a three-fold increase in lamellipodia either in cells cultured under differentiated or undifferentiated growth conditions. In undifferentiated N2A cells, SOD1 constructs promoted lamellipodial protrusions to similar extent as the overexpression of Rac1, and SOD1-mediated lamellipodia were prevented by coexpression of the N17 dominant-negative form of Rac1, or shRNA for a downstream effector of Rac1, the insulin receptor tyrosine kinase substrate p53 (IRSp53) or its binding partner LIN7. Moreover, no additive effect was measured by coexpression of the SOD1 constructs with Rac1, IRSp53 or LIN7. Collectively these data support a role for SOD1 in the regulation of Rac1-mediated lamellipodia pathway, a property fully retained by the two SOD1 mutants.

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“…Within the soma of a mammalian neuron, CASK can be found in a distinct punctate (organelle) distribution [ 54 ]. It has been suggested that CASK is localized to the endoplasmic reticulum, whereas its interactor Mint-1 (lin-10) has been localized to the Golgi complex and veli (lin-7) has been found on mitochondria [ 70 , 102 , 103 ]. Multiple studies have identified CASK as a probable constituent of mitochondria-associated membrane [ 104 , 105 ].…”

Section: The Molecular Function Of Caskmentioning

confidence: 99%

The Non-Linear Path from Gene Dysfunction to Genetic Disease: Lessons from the MICPCH Mouse Model

Mukherjee

LaConte

Srivastava

2022

Cells

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Most human disease manifests as a result of tissue pathology, due to an underlying disease process (pathogenesis), rather than the acute loss of specific molecular function(s). Successful therapeutic strategies thus may either target the correction of a specific molecular function or halt the disease process. For the vast majority of brain diseases, clear etiologic and pathogenic mechanisms are still elusive, impeding the discovery or design of effective disease-modifying drugs. The development of valid animal models and their proper characterization is thus critical for uncovering the molecular basis of the underlying pathobiological processes of brain disorders. MICPCH (microcephaly and pontocerebellar hypoplasia) is a monogenic condition that results from variants of an X-linked gene, CASK (calcium/calmodulin-dependent serine protein kinase). CASK variants are associated with a wide range of clinical presentations, from lethality and epileptic encephalopathies to intellectual disabilities, microcephaly, and autistic traits. We have examined CASK loss-of-function mutations in model organisms to simultaneously understand the pathogenesis of MICPCH and the molecular function/s of CASK. Our studies point to a highly complex relationship between the potential molecular function/s of CASK and the phenotypes observed in model organisms and humans. Here we discuss the implications of our observations from the pathogenesis of MICPCH as a cautionary narrative against oversimplifying molecular interpretations of data obtained from genetically modified animal models of human diseases.

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Novel localisation and possible function of LIN7 and IRSp53 in mitochondria of HeLa cells

Cited by 6 publications

References 43 publications

BVVL/ FL: features caused by SLC52A3 mutations; WDFY4 and TNFSF13B may be novel causative genes

BVVL/ FL: features caused by SLC52A3 mutations; WDFY4 and TNFSF13B may be novel causative genes

SOD1 stimulates lamellipodial protrusions in Neuro 2A cell lines

The Non-Linear Path from Gene Dysfunction to Genetic Disease: Lessons from the MICPCH Mouse Model

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