The cerebellar leucine-rich acidic nuclear protein interacts with ataxin-1

Abstract

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder characterized by ataxia, progressive motor deterioration, and loss of cerebellar Purkinje cells. SCA1 belongs to a growing group of neurodegenerative disorders caused by expansion of CAG repeats, which encode glutamine. Although the proteins containing these repeats are widely expressed, the neurodegeneration in SCA1 and other polyglutamine diseases selectively involves a few neuronal subtypes. The mechanism(s) underlying this neuronal specificity is unknown. Here we show that the cerebellar leucine-rich acidic nuclear protein (LANP) interacts with ataxin-1, the SCA1 gene product. LANP is expressed predominantly in Purkinje cells, the primary site of pathology in SCA1. The interaction between LANP and ataxin-1 is significantly stronger when the number of glutamines is increased. Immunofluorescence studies demonstrate that both LANP and ataxin-1 colocalize in nuclear matrix-associated subnuclear structures. The features of the interaction between ataxin-1 and LANP, their spatial and temporal patterns of expression, and the colocalization studies indicate that cerebellar LANP is involved in the pathogenesis of SCA1.

Ataxin 1, a SCA1 neurodegenerative disorder protein, is functionally linked to the silencing mediator of retinoid and thyroid hormone receptors

“…Additionally, SMRT forms nuclear foci (13,14) that resemble those formed by Atx1 (15,16). These observations led us to hypothesize that SMRT and SMRTER may interact with Atx1.…”

Mapping the self-association domains of ataxin-1: Identification of novel non overlapping motifs

“…A self-association region of the non-expanded protein was mapped in the centre of the protein and identified to overlap the only certified globular domain of the otherwise PeerJ PrePrints | http://dx.doi.org/10.7287/peerj.preprints.259v1 | CC-BY 4.0 Open Access | received: , published: 27 Feb 2014 mostly unstructured protein, the AXH domain that spans residues 562-689 (SMART SM00536) (Burright et al, 1997;de Chiara et al, 2003). This motif is functionally very important as it is involved in transcriptional regulation as well as in the RNA-binding activity of ataxin-1 (Matilla et al, 1997;Okazawa et al 2002;Tsai et al, 2004;de Chiara et al, 2003;de Chiara et al, 2005;Mizutani et al, 2005;Tsuda et al 2005;Lam et al, 2006;Serra et al, 2006;Goold et al, 2007;Lee et al 2011). AXH is also necessary and sufficient for the majority of the known interactions of ataxin-1 with other proteins, most of which are transcriptional regulators (Tsai et al, 2004;Tsuda et al 2005;Lam et al, 2006;Goold et al, 2007;Serra et al, 2006).…”

Transgenic models and subcellular pathology — do they tell us what goes wrong in Huntington's disease?

“…It is shown that the ataxin-1 binds to a protein, leucinerich acidic nuclear protein (LANP) that is expressed predominantly in the neurons that are particularly affected in SCA1, the Purkinje cells. 23 This interaction is stronger as the polyglutamine sequence of ataxin-1 increases, and it is conceivable that the interaction between LANP and ataxin-1 results in NII formation and eventually neuronal pathology in SCA1. By analogy with these findings, it could be valuable to identify possible interactions between the expanded HD gene product and proteins specific to nuclei of neurons degenerating in HD, for example, GABAergic striatal neurons.…”