Structural and Functional Evaluation of C. elegans Filamins FLN-1 and FLN-2

DeMaso, Christina R.; Kovacevic, Ismar; Uzun, Alper; Cram, Erin J.

doi:10.1371/journal.pone.0022428

Cited by 19 publications

(20 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our previous work described the C. elegans filamin orthologs, and established that FLN-1 is required for function of the spermatheca, a smooth muscle-like tissue in the C. elegans gonad [27], [28]. Filamin-deficient spermathecae are unable to constrict, and as a result trap fertilized embryos [27].…”

Section: Discussionmentioning

confidence: 99%

“…Our previous work focused on the initial characterization of a well-conserved C. elegans filamin ortholog FLN-1 [27], [28]. FLN-1 consists of an N-terminal ABD followed by 20 IgFLN domains, and is expressed in the spermatheca and uterus, where it colocalizes with F-actin [27], [28].…”

Section: Introductionmentioning

confidence: 99%

“…FLN-1 consists of an N-terminal ABD followed by 20 IgFLN domains, and is expressed in the spermatheca and uterus, where it colocalizes with F-actin [27], [28]. The allele fln-1(tm545) deletes a portion of the ABD, and a frameshift disrupts translation of all 20 of the IgFLN domains.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Filamin and Phospholipase C-ε Are Required for Calcium Signaling in the Caenorhabditis elegans Spermatheca

2013

Self Cite

View full text Add to dashboard Cite

The Caenorhabditis elegans spermatheca is a myoepithelial tube that stores sperm and undergoes cycles of stretching and constriction as oocytes enter, are fertilized, and exit into the uterus. FLN-1/filamin, a stretch-sensitive structural and signaling scaffold, and PLC-1/phospholipase C-ε, an enzyme that generates the second messenger IP3, are required for embryos to exit normally after fertilization. Using GCaMP, a genetically encoded calcium indicator, we show that entry of an oocyte into the spermatheca initiates a distinctive series of IP3-dependent calcium oscillations that propagate across the tissue via gap junctions and lead to constriction of the spermatheca. PLC-1 is required for the calcium release mechanism triggered by oocyte entry, and FLN-1 is required for timely initiation of the calcium oscillations. INX-12, a gap junction subunit, coordinates propagation of the calcium transients across the spermatheca. Gain-of-function mutations in ITR-1/IP3R, an IP3-dependent calcium channel, and loss-of-function mutations in LFE-2, a negative regulator of IP3 signaling, increase calcium release and suppress the exit defect in filamin-deficient animals. We further demonstrate that a regulatory cassette consisting of MEL-11/myosin phosphatase and NMY-1/non-muscle myosin is required for coordinated contraction of the spermatheca. In summary, this study answers long-standing questions concerning calcium signaling dynamics in the C. elegans spermatheca and suggests FLN-1 is needed in response to oocyte entry to trigger calcium release and coordinated contraction of the spermathecal tissue.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Filamin and Phospholipase C-ε Are Required for Calcium Signaling in the Caenorhabditis elegans Spermatheca

2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…The Caenorhabditis elegans filamin, FLN1, is also composed of an N-terminal ABD followed by 20 Ig domains, although two other filamin isoforms with C- and N-terminal truncations can also be formed (66). A second C. elegans filamin ortholog , FLN-2 (17), and the Drosophila filamin-related protein encoded by jitterbug ( jbug ) (118) have some distinct features not found in vertebrates including an ABD consisting of three CH-domains and several non-conserved stretches between IgFLNs (17, 65). …”

Section: Filaminsmentioning

confidence: 99%

Filamins in Mechanosensing and Signaling

Razinia

Mäkelä

Ylänne

et al. 2012

Annu. Rev. Biophys.

229

251

View full text Add to dashboard Cite

Filamins are essential, evolutionary conserved, modular, multi-domain, actin-binding proteins that organize the actin cytoskeleton and maintain extracellular matrix connections by anchoring actin filaments to transmembrane receptors. By crosslinking and anchoring actin filaments, filamins stabilize the plasma membrane, provide cellular cortical rigidity and contribute to the mechanical stability of the plasma membrane and the cell cortex. In addition to actin, filamins interact with over 90 other binding partners including intracellular signaling molecules, receptors, ion channels, transcriptions factors and cytoskeletal and adhesion proteins. Thus, filamins scaffold a wide range of signaling pathways and are implicated in the regulation of a diverse array of cellular functions including motility, maintenance of cell shape and differentiation. Here, we review emerging structural and functional evidence that filamins are mechanosensors and/or mechanotransducers, playing essential roles in helping cells to detect and respond to physical forces in their local environment.

show abstract

“…In mammalian muscle, filamin localizes to the Z-discs [59], and mutations in the human filamin gene FLNC cause several types of myopathies in skeletal muscle and cardiomyopathies [60][61][62][63]. Interestingly, C. elegans has two filamin genes [64] but their functions in muscle have not been characterized. Thus, further functional studies on kettin and filamin in C. elegans should provide insight into the fundamental roles of actin-binding proteins with Ig domains during assembly and maintenance of myofibrils.…”

Section: Discussionmentioning

confidence: 99%

Kettin, the large actin‐binding protein with multiple immunoglobulin domains, is essential for sarcomeric actin assembly and larval development in Caenorhabditis elegans

et al. 2019

View full text Add to dashboard Cite

Among many essential genes in the nematode Caenorhabditis elegans, let‐330 is located on the left arm of chromosome V and was identified as the largest target of a mutagen in this region. However, let‐330 gene has not been characterized at the molecular level. Here, we report that two sequenced let‐330 alleles are nonsense mutations of ketn‐1, a previously characterized gene encoding kettin. Kettin is a large actin‐binding protein of 472 kDa with 31 immunoglobulin domains and is expressed in muscle cells in C. elegans. let‐330/ketn‐1 mutants are homozygous lethal at the first larval stage with mild defects in body elongation. These mutants have severe defects in sarcomeric actin and myosin assembly in striated muscle. However, α‐actinin and vinculin, which are components of the dense bodies anchoring actin to the membranes, were not significantly disorganized by let‐330/ketn‐1 mutation. Kettin localizes to embryonic myofibrils before α‐actinin is expressed, and α‐actinin deficiency does not affect kettin localization in larval muscle. Depletion of vinculin minimally affects kettin localization but significantly reduces colocalization of actin with kettin in embryonic muscle cells. These results indicate that kettin is an essential protein for sarcomeric assembly of actin filaments in muscle cells.

show abstract

Structural and Functional Evaluation of C. elegans Filamins FLN-1 and FLN-2

Cited by 19 publications

References 68 publications

Filamin and Phospholipase C-ε Are Required for Calcium Signaling in the Caenorhabditis elegans Spermatheca

Filamin and Phospholipase C-ε Are Required for Calcium Signaling in the Caenorhabditis elegans Spermatheca

Filamins in Mechanosensing and Signaling

Kettin, the large actin‐binding protein with multiple immunoglobulin domains, is essential for sarcomeric actin assembly and larval development in Caenorhabditis elegans

Contact Info

Product

Resources

About