EML proteins in microtubule regulation and human disease

Abstract

The EMLs are a conserved family of microtubule-associated proteins (MAPs). The founding member was discovered in sea urchins as a 77-kDa polypeptide that co-purified with microtubules. This protein, termed EMAP for echinoderm MAP, was the major non-tubulin component present in purified microtubule preparations made from unfertilized sea urchin eggs [J. Cell Sci. (1993) 104, 445–450; J. Cell Sci. (1987) 87(Pt 1), 71–84]. Orthologues of EMAP were subsequently identified in other echinoderms, such as starfish and sand dollar, and then in more distant eukaryotes, including flies, worms and vertebrates, where the name of ELP or EML (both for EMAP-like protein) has been adopted [BMC Dev. Biol. (2008) 8, 110; Dev. Genes Evol. (2000) 210, 2–10]. The common property of these proteins is their ability to decorate microtubules. However, whether they are associated with particular microtubule populations or exercise specific functions in different microtubule-dependent processes remains unknown. Furthermore, although there is limited evidence that they regulate microtubule dynamics, the biochemical mechanisms of their molecular activity have yet to be explored. Nevertheless, interest in these proteins has grown substantially because of the identification of EML mutations in neuronal disorders and oncogenic fusions in human cancers. Here, we summarize our current knowledge of the expression, localization and structure of what is proving to be an interesting and important class of MAPs. We also speculate about their function in microtubule regulation and highlight how the studies of EMLs in human diseases may open up novel avenues for patient therapy.

Spatiotemporal gene expression patterns reveal molecular relatedness between retinal laminae

“…For example, amacrine‐specific genes would be predicted to be present in the lower half of the INL and in ~40% of the GCL, while amacrine subtype‐specific genes might be present only in a subset of INL neurons. Four genes robustly displayed one of these patterns by lacZ staining: echinoderm microtubule‐associated protein‐like 2 ( Eml2 , Fry, O'Regan, Montgomery, Adib, & Bayliss, ), fibroblast growth factor 3 ( Fgf3 , Represa, Leon, Miner, & Giraldez, ), Phf24 , and Dbn1 . To further explore these patterns, we focused our analysis on Dbn1 .…”

Mutations in the Heterotopia Gene Eml1/EML1 Severely Disrupt the Formation of Primary Cilia

“…Centrosome-Primary Cilia Phenotype EML1 has a cell-cycle-dependent localization in mouse neuronal progenitor cells in vitro (Kielar et al, 2014). It co-localizes with the microtubule network in interphase Vero cells (Kielar et al, 2014); however, a ciliary localization has not been described for this protein family (Fry et al, 2016). Its localization was hence further explored in aRGs, as well as in ciliated RPE1 cells, using exogenous expression of an EML1-tagged plasmid, since there are no known reliable antibodies to detect the endogenous protein.…”

EML4-ALK Variants: Biological and Molecular Properties, and the Implications for Patients

“…In the second study, the structure of the coiled-coil region of EML2 and EML4 revealed that these regions were required for trimeric oligomerisation, and this was named the trimerisation domain (TD) [ 15 ]. It is through the TD and the basic region that EML proteins are able to associate with microtubules, although it is not yet known whether this is through direct binding or via oligomerisation [ 15 , 16 ]. In addition, the TAPE domain is able to bind soluble α/β-tubulin heterodimers through its concave surface, but again, further work is required to understand the importance of this interaction [ 14 ].…”