Disease relevance of NDEL1

• Grp170 contains an ATP binding domain and binds ATP, it possesses a carboxyl terminal NDEL sequence, and its mRNA is anoxia inducible [1].
• Subtypes of HLA-DRB1*03, *08, *11, *12, *13 and *14 in early onset pauciarticular juvenile chronic arthritis (EOPA) with and without iridocyclitis [2].

Psychiatry related information on NDEL1

• Together, it is concluded that Nudel is critical for dynein motor activity in membrane transport and possibly other cellular activities through interactions with both Lis1 and dynein heavy chain [3].

High impact information on NDEL1

• 14-3-3epsilon binds to CDK5/p35-phosphorylated NUDEL and this binding maintains NUDEL phosphorylation [4].
• These proteins play a crucial role in centrosome positioning, with Nde1 functioning mainly during progenitor cell divisions and Ndel1 functioning in neuronal migration [5].
• These results provide strong evidence that Ndel1 interacts with LIS1 to sustain the function of dynein, which in turn impacts microtubule organization, nuclear translocation, and neuronal positioning [6].
• Here we characterize NUDEL, a novel LIS1-interacting protein with sequence homology to gene products also implicated in nuclear distribution in fungi [7].
• Nudel functions in membrane traffic mainly through association with Lis1 and cytoplasmic dynein [3].

Biological context of NDEL1

• Our results suggest that NDEL1 is essential for mitotic cell division and neuronal migration not only via regulation of cytoplasmic dynein function but also by modulation of katanin p60 localization and function [8].
• The NDEL1 binding site of DISC1 was narrowed down to a small portion of exon 13, corresponding to amino acids 802-835 of DISC1 [9].
• Nudel and Lis1 appear to regulate cytoplasmic dynein in neuronal migration and mitosis through direct interactions [3].
• Moreover, silencing Nudel expression by RNA interference results in Golgi apparatus fragmentation and cell death [3].
• Human Nudel and NudE as regulators of cytoplasmic dynein in poleward protein transport along the mitotic spindle [10].

Anatomical context of NDEL1

• Among several components of the dynein motor complex, DISC1 and NDEL1 are selectively upregulated during neurite outgrowth upon differentiation in PC12 cells [9].
• Here, we show that a specific interaction between DISC1 and nuclear distribution element-like (NDEL1/NUDEL) is required for neurite outgrowth in differentiating PC12 cells [9].
• Like LIS1, NUDEL is robustly expressed in brain, enriched at centrosomes and neuronal growth cones, and interacts with cytoplasmic dynein [7].
• NDEL1 is a binding partner of LIS1 that participates in the regulation of cytoplasmic dynein function and microtubule organization during mitotic cell division and neuronal migration [11].
• Herein, overexpression of a Nudel mutant defective in association with either Lis1 or dynein heavy chain is shown to cause dispersions of membranous organelles whose trafficking depends on dynein [3].

Associations of NDEL1 with chemical compounds

• Genetic and molecular studies have suggested that the Nudel protein is also functionally modular, with a serine protease domain that is specifically required for ventral development [12].
• Amino acid sequence of CBP-140 contains a carboxyl-terminal Asn-Asp-Glu-Leu (NDEL) sequence, which resembles Lys-Asp-Glu-Leu (KDEL) sequence, a signal to retain the resident proteins in endoplasmic reticulum; NDEL sequence may indeed play a similar role [13].

Physical interactions of NDEL1

• Furthermore, Nudel can interact with pericentrin independently of dynein [14].

Enzymatic interactions of NDEL1

• Interestingly, NDEL1 phosphorylated by Aurora-A was rapidly downregulated thereafter by ubiquitination-mediated protein degradation [11].

Regulatory relationships of NDEL1

• Together, these results indicate that DISC1 regulates the localization of NUDEL/LIS1/14-3-3epsilon complex into the axons as a cargo receptor for axon elongation [15].

Other interactions of NDEL1

• Bioinformatic analysis revealed the nud-2 gene, encoding the worm homolog of mammalian effectors of LIS1, termed NDE1 and NDEL1 [16].
• Recent studies have suggested that DISC1 plays a role in neuronal outgrowth, possibly through reported interactions with the molecules Nudel and FEZ1 [17].
• In addition, NDEL1 is required for centrosome targeting of TACC3 through the interaction with TACC3 [11].
• Our findings suggest that Aurora-A-mediated phosphorylation of NDEL1 is essential for centrosomal separation and centrosomal maturation and for mitotic entry [11].
• During centriole duplication, Nudel targets to the new mother centriole later than ninein but earlier than dynactin [14].

Analytical, diagnostic and therapeutic context of NDEL1

• A chimeric plasmid containing about 2/3 of the rat skeletal muscle actin gene plus 730 base pairs of its 5' flanking sequences fused to the 3' end of a human embryonic globin gene (D. Melloul, B. Aloni, J. Calvo, D. Yaffe, and U. Nudel, EMBO J. 3:983-990, 1984) was inserted into mice by microinjection into fertilized eggs [18].

References