Illuminating the dark kinome: utilizing multiplex peptide activity arrays to functionally annotate understudied kinases.

Protein kinases are critical components of a myriad biological processes and strongly associated with various diseases. While kinase research has been a point of focus in biomedical research for several decades, a large portion of the kinome is still considered understudied or "dark," because prior research is targeted towards a subset of kinases with well-established roles in cellular processes. We present an empirical and in-silico hybrid workflow to extend the functional knowledge of understudied kinases.

Neuronal alterations in AKT isotype expression in schizophrenia.

Schizophrenia is characterized by substantial alterations in brain function, and previous studies suggest insulin signaling pathways, particularly involving AKT, are implicated in the pathophysiology of the disorder. This study demonstrates elevated mRNA expression of AKT1-3 in neurons from schizophrenia subjects, contrary to unchanged or diminished total AKT protein expression reported in previous postmortem studies, suggesting a potential decoupling of transcript and protein levels. Sex-specific differential AKT activity was observed, indicating divergent roles in males and females with schizophrenia.

Comparative analysis of the MyTH4-FERM myosins reveals insights into the determinants of actin track selection in polarized epithelia.

MyTH4-FERM (MF) myosins evolved to play a role in the creation and function of a variety of actin-based membrane protrusions that extend from cells. Here we performed an analysis of the MF myosins, Myo7A, Myo7B, and Myo10, to gain insight into how they select for their preferred actin networks. Using enterocytes that create spatially separated actin tracks in the form of apical microvilli and basal filopodia, we show that actin track selection is principally guided by the mode of oligomerization of the myosin along with the identity of the motor domain, with little influence from the specific composition of the lever arm.

A cryptic sequence targets the adhesion complex scaffold ANKS4B to apical microvilli to promote enterocyte brush border assembly.

Nutrient-transporting enterocytes interact with their luminal environment using a densely packed collection of apical microvilli known as the brush border. Assembly of the brush border is controlled by the intermicrovillar adhesion complex (IMAC), a protocadherin-based complex found at the tips of brush border microvilli that mediates adhesion between neighboring protrusions. ANKS4B is known to be an essential scaffold within the IMAC, although its functional properties have not been thoroughly characterized.