Data from: Expression, subcellular localization, and mechanistic analysis of intellectual disability syndrome protein ABBA

A missense mutation in the MTSS2 gene, which encodes the I-BAR domain
protein ABBA (Mtss1l/Mtss2), has been linked to an intellectual disability
syndrome. To better understand the MTSS2 mutation-related effect in the
brain, we elucidated the cells expressing ABBA and the localization of
ABBA in these cells to get insights into which cells and processes might
be dysfunctional in mutation-carrying patients. As a novel discovery, we
found that ABBA was highly expressed in GABAergic inhibitory neurons, such
as parvalbumin-positive interneurons in the hippocampus. At the
subcellular level, ABBA localizes to the edges of membrane protrusions in
various cells in the brain, suggesting a role in cell migration and
spinogenesis. Overexpression of ABBA in pyramidal excitatory and
inhibitory neurons increased dendritic spine density. Through live-cell
imaging, we demonstrated that ABBA facilitates spine initiation by
clustering on the plasma membrane before a new filopodium appears.
However, our live cell imaging data also revealed that ABBA localized not
only to small focal points, typical for filopodia formation, on the plasma
membrane, but also more broadly on the edge of lamellipodial structures.
Compared to its close homolog MIM, ABBA appears to be a more general
facilitator of protrusion formation, from dendritic filopodia to
lamellipodial structures. Altogether, our findings provide insights into
ABBA expression, localization, and functional mechanisms, advancing our
understanding of its role in neurodevelopmental processes and disorders.