EML proteins in microtubule regulation and human disease.

Andrew M Fry,Jessica Montgomery,Laura O'Regan,Rozita Adib,Richard Bayliss

doi:10.1042/bst20160125

Andrew M Fry, Jessica Montgomery + Show 3 more

Open Access

https://doi.org/10.1042/bst20160125

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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.

Highlights

The EMLs are a conserved family of microtubule‐associated proteins (MAPs)
We speculate about their function in microtubule regulation and highlight how studies of EMLs in human diseases may open up novel avenues for patient therapy
Expression analyses reveal that EML1 and EML4 are highly expressed in early mouse embryos, but exhibit a lower and more restricted expression pattern in late embryos and adults with the most common site of expression being the nervous system, including the hippocampus, cortex, cerebellum, eyes and olfactory bulb (Houtman et al, 2007; Kielar et al, 2014)

Summary

EML PROTEINS IN MICROTUBULE REGULATION AND HUMAN DISEASE

The second propeller is assembled from 6 WD repeats and an additional sub‐domain that is formed from separate regions of the primary sequence of EML1. This domain appears to be a ubiquitous and unique feature of EML family proteins, and was termed the TAPE (tandem atypical propeller in EML) domain. Crystal structures of the coiled‐coil regions of human EML2 and EML4 were determined to resolutions of 2.1 Å and 2.9 Å, respectively (Figure 2B) In both structures, three molecules of the EML protein come together through a core of hydrophobic interactions stabilized by salt‐bridges to form a trimerization domain (Figure 2C). EML1‐4 are all trimeric, coprecipitation experiments indicate that these proteins have the potential to assemble heterotrimers, as well as homotrimers (Richards et al, 2015)

Microtubule binding and regulation of EMLs

EML functions in differentiated and proliferating cells

EMLs in human disease

Future perspectives

Findings

FIGURE LEGENDS