The ERM (
ezrin,
radixin, and
moesin)
proteins belong to the band-4.1 superfamily of membrane-cytoskeleton-linking
proteins which bind to the actin cytoskeleton via their C-terminal sequences and bind ERM binding
membrane proteins (ERMBMPs). We investigated the immunohistochemical expression of two of the ERM
proteins (
ezrin and
moesin) in developing human cerebral cortex and in cortical tubers from patients with
tuberous sclerosis (
TSC), to assess possible consequences of
TSC gene product malfunction or inactivation in the developing brain in relation to ERM
protein expression.
Ezrin is abundantly expressed within radial glia and migrating cells in the intermediate zone in the prenatal human cerebrum, while
moesin is primarily expressed in vascular endothelial cells in developing and adult human brain and scattered microglia in adult brain. In addition, both
ezrin and
moesin are abundantly co-expressed with
hamartin and
tuberin within a population of abnormal cells in
TSC-associated cortical tubers. The expression of these two
proteins--primarily
ezrin--suggests that they are developmentally regulated and abundantly expressed in germinal matrix and/or migrating cells during cerebral cortical development. In
TSC-associated cortical tubers, both
proteins appeared to be up-regulated and are co-localized within a population of abnormal neuroglial cells typical of those seen in tubers. Expression of these
proteins and their co-localization with
tuberin and
hamartin in these cells may suggest a compensatory up-regulation in response to
TSC gene mutation.