Unusual splicing events result in distinct Xin isoforms that associate differentially with filamin c and Mena/VASP

Ven, Peter F.M. van der; Ehler, Elisabeth; Vakeel, Padmanabhan; Eulitz, Stefan; Schenk, Jörg A.; Milting, Hendrik; Micheel, Burkhard; Fürst, Dieter O.

doi:10.1016/j.yexcr.2006.03.015

Cited by 85 publications

(120 citation statements)

References 67 publications

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“…15 Xin plays an important role in the molecular mechanism involved in developmental and adaptive remodeling of the actin cytoskeleton during cardiac morphogenesis and sarcomere assembly. 12 Recently, CMYA1 has been reported to be a CAN-gene in pancreatic cancer in addition to breast and colorectal cancers.…”

Section: Resultsmentioning

confidence: 99%

Multiple tumor-suppressor genes on chromosome 3p contribute to head and neck squamous cell carcinoma tumorigenesis

Lee

Schönleben

Banuchi

et al. 2010

Cancer Biology & Therapy

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Section: Resultsmentioning

confidence: 99%

Multiple tumor-suppressor genes on chromosome 3p contribute to head and neck squamous cell carcinoma tumorigenesis

Lee

Schönleben

Banuchi

et al. 2010

Cancer Biology & Therapy

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“…Since the mutation in the Ky gene in the mouse is associated with an abnormal distribution of its binding partner FLNC and Xin, 12,13 which is a FLNC-binding partner 10 and general muscle damage marker, 14 we stained skeletal muscle sections of our patient for both proteins. Even though some parts of the sections appeared largely unaffected, in other areas inclusions containing the proteins were seen inside the fibers, with an incidence ranging from mild (fibers with mostly small inclusions) to severe (numerous fibers affected and very large inclusions) (Supplementary Figure S1).…”

Section: Muscle Pathologymentioning

confidence: 99%

A new early-onset neuromuscular disorder associated with kyphoscoliosis peptidase (KY) deficiency

et al. 2016

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We describe a new early-onset neuromuscular disorder due to a homozygous loss-of-function variant in the kyphoscoliosis peptidase gene (KY). A 7.5-year-old girl with walking difficulties from 2 years of age presented with generalized muscle weakness; mild contractures in the shoulders, hips and feet; cavus feet; and lordosis but no scoliosis. She had previously been operated with Achilles tendon elongation. Whole-body MRI showed atrophy and fatty infiltration in the calf muscles. Biopsy of the vastus lateralis muscle showed variability in fiber size, with some internalized nuclei and numerous very small fibers with variable expression of developmental myosin heavy chain isoforms. Some small fibers showed abnormal sarcomeres with thickened Z-discs and small nemaline rods. Whole-exome sequencing revealed a homozygous one-base deletion (c.1071delG, p.(Thr358Leufs*3)) in KY, predicted to result in a truncated protein. Analysis of an RNA panel showed that KY is predominantly expressed in skeletal muscle in humans. A recessive variant in the murine ortholog Ky was previously described in a spontaneously generated mouse mutant with kyphoscoliosis, which developed postnatally and was caused by dystrophy of postural muscles. The abnormal distribution of Xin and Ky-binding partner filamin C in the muscle fibers of our patient was highly similar to their altered localization in ky/ky mouse muscle fibers. We describe the first human case of disease associated with KY inactivation. As in the mouse model, the affected child showed a neuromuscular disorder -but in contrast, no kyphoscoliosis.

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“…Xin␣; myotendinous junction; muscle fatigue; fast troponin T fragmentation THE FAMILY OF XIN REPEAT-CONTAINING proteins is a relatively new class of actin-binding protein primarily found in striated muscle cells (10,19,33,44,57,59,62). The majority of Xin proteins in muscle cells is present in adherence junctions: the intercalated disc of cardiac muscle and the myotendinous junction (MTJ) of skeletal muscle (20,44,49,57,59).…”

mentioning

confidence: 99%

“…The majority of Xin proteins in muscle cells is present in adherence junctions: the intercalated disc of cardiac muscle and the myotendinous junction (MTJ) of skeletal muscle (20,44,49,57,59). In mammals, a pair of paralogous genes encodes two protein isoforms, Xin␣ [also called cardiomyopathy-associated 1 (Cmya1) or Xin actin-binding repeat-containing 1 (Xirp1)] and Xin␤ (also called Cmya3, myomaxin, or Xirp2; Ref.…”

mentioning

confidence: 99%

Localization and function of Xinα in mouse skeletal muscle

Feng

Wang

Reiter

et al. 2013

American Journal of Physiology-Cell Physiology

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The Xin repeat-containing proteins were originally found in the intercalated discs of cardiac muscle with implicated roles in cardiac development and function. A pair of paralogous genes, Xin␣ (Xirp1) and Xin␤ (Xirp2), is present in mammals. Ablation of the mouse Xin␣ (mXin␣) did not affect heart development but caused late-onset adulthood cardiac hypertrophy and cardiomyopathy with conductive defects. Both mXin␣ and mXin␤ are also found in the myotendinous junction (MTJ) of skeletal muscle. Here we investigated the structural and functional significance of mXin␣ in skeletal muscle. In addition to MTJ and the contact sites between muscle and perimysium, mXin␣ but not mXin␤ was found in the blood vessel walls, whereas both proteins were absent in neuromuscular junctions and nerve fascicles. Coimmunoprecipitation suggested association of mXin␣ with talin, vinculin, and filamin, but not ␤-catenin, in adult skeletal muscle, consistent with our previous report of colocalization of mXin␣ with vinculin. Loss of mXin␣ in mXin␣-null mice had subtle effects on the MTJ structure and the levels of several MTJ components. Diaphragm muscle of mXin␣-null mice showed hypertrophy. Compared with wild-type controls, mouse extensor digitorum longus (EDL) muscle lacking mXin␣ exhibited no overt change in contractile and relaxation velocities or maximum force development but better tolerance to fatigue. Loaded fatigue contractions generated stretch injury in wild-type EDL muscle as indicated by a fragmentation of troponin T. This effect was blunted in mXin␣-null EDL muscle. The results suggest that mXin␣ play a role in MTJ conductance of contractile and stretching forces.

show abstract

Unusual splicing events result in distinct Xin isoforms that associate differentially with filamin c and Mena/VASP

Cited by 85 publications

References 67 publications

Multiple tumor-suppressor genes on chromosome 3p contribute to head and neck squamous cell carcinoma tumorigenesis

Multiple tumor-suppressor genes on chromosome 3p contribute to head and neck squamous cell carcinoma tumorigenesis

A new early-onset neuromuscular disorder associated with kyphoscoliosis peptidase (KY) deficiency

Localization and function of Xinα in mouse skeletal muscle

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