EVH1 Domains

Listeria monocytogenes infections are a common cause of food poisoning, and an effective means to block their infectivity is highly desirable. These pathogens contain a protein called ActA that contains four EVH1 FPPPP consensus motifs and that effectively hijacks the EVH1-containing proteins Ena and VASP (Chakraborty et al. 1995). EVH1-mediated actin binding allows the bacterium to propel itself along the cell's actin cytoskeleton, leaving behind a so-called actin-rich "comet tail" and thus allowing the pathogen to move rapidly through a cell's cytoplasm. Deletion of the FPPP motifs in ActA or injection of FPPPP-containing peptide into the cytoplasm strongly reduces the motility of Listeria (Southwick and Purich 1994), and small-molecule mimetics of the FPPPP motif would represent an important step towards a Listeria-targeting drug.

Another interesting class of proteins containing EVH1 domains is the Homer proteins (Shiraishi-Yamaguchi and Furuichi 2007). These proteins are implicated in the formation of oligomeric structures of the post-synaptic density matrix and thereby contribute to synaptogenesis and receptor trafficking. In addition, Homer proteins are directly involved in controlling glutamate levels in the limbo-corticostriatal regions of the brain. Studies of Homer knock-out mice revealed involvement of these proteins in a number of behavioral abnormalities and neu-ropsychatric disorders, such as addiction, depression, epilepsy and schizophrenia (Szumlinski et al. 2006). Homer 2 knockout and overexpression studies in mice, for example, reveal a positive role of the protein in behavior leading to increased alcohol consumption (Szumlinski et al. 2005). The role of the EVH1 domain in the development of these diseases is not understood, but specific inhibition of Homer EVH1 domains would enable their function to be studied and may provide useful lead compounds for the development of drugs to be used in the context of neurobe-havioral disorders.

Alcohol No More

Alcohol No More

Do you love a drink from time to time? A lot of us do, often when socializing with acquaintances and loved ones. Drinking may be beneficial or harmful, depending upon your age and health status, and, naturally, how much you drink.

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