The poly-proline motifs found in the cytoplasmic tail of the brush border cadherin CDHR5 play a role in its ability to elongate microvilli.

Cadherin-related family member 5 (CDHR5) is a protocadherin found enriched at the tips of brush border microvilli of the gut and kidney, where it plays an important role in the development of these specialized microvilli. CDHR5 is a type-1 transmembrane protein with a short cytoplasmic tail that contains a number of poly-proline motifs of unknown function. We performed an analysis of the poly-proline stretches in the CDHR5 cytoplasmic tail and show that mutation of these motifs does not largely influence the targeting of CDHR5 to microvilli, but does significantly impact the ability of the cadherin to promote microvillar elongation.

CDHR5 splice isoform cooperation promotes apical targeting of the brush border cadherin.

Cadherin-related family member 5 (CDHR5) is an adhesion molecule that is highly enriched in the microvilli found on the surface of transporting epithelial cells of the gut and kidney. CDHR5 localizes to the distal tips of these microvilli as part of an adhesion complex that drives assembly of microvilli into a cohesive apical brush border, a hallmark feature of polarized transporting epithelial cells. Loss of CDHR5 correlates with poor prognosis of colon cancer patients, while forced over-expression of CDHR5 in colorectal cancer cell lines blocks their ability to form tumors in mice.

Repeat-element RNAs integrate a neuronal growth circuit.

Neuronal growth and regeneration are regulated by local translation of mRNAs in axons. We examined RNA polyadenylation changes upon sensory neuron injury and found upregulation of a subset of polyadenylated B2-SINE repeat elements, hereby termed GI-SINEs (growth-inducing B2-SINEs). GI-SINEs are induced from ATF3 and other AP-1 promoter-associated extragenic loci in injured sensory neurons but are not upregulated in lesioned retinal ganglion neurons.

Select autosomal dominant DFNA11 deafness variants activate Myo7A targeting in epithelial cells.

Myosin-7A (Myo7A) is a motor protein crucial for the organization and function of stereocilia, specialized actin-rich protrusions on the surface of inner ear hair cells that mediate hearing. Variants in Myo7A cause several forms of genetic hearing loss, including autosomal dominant DFNA11 deafness. Despite its importance, the structural elements that control Myo7A within cells are not well understood.

KHSRP-mediated Decay of Axonally Localized Prenyl-Cdc42 mRNA Slows Nerve Regeneration.

The small GTPase CDC42 promotes axon growth through actin filament polymerization and this growth is driven by axonal localization of the mRNA encoding the prenylated CDC42 isoform (). Here, we show that axonal mRNA transport and translation are decreased by growth-inhibiting stimulation and increased by growth-promoting stimulation. In contrast, axonal mRNA transport and translation are increased by growth inhibition but unaffected by growth promotion.

The microvillar protocadherin CDHR5 associates with EBP50 to promote brush border assembly.

Transporting epithelial cells of the gut and kidney interact with their luminal environment through a densely packed collection of apical microvilli known as a brush border (BB). Proper brush border assembly depends on the intermicrovillar adhesion complex (IMAC), a protocadherin-based adhesion complex found at the distal tips of microvilli that mediates adhesion between neighboring protrusions to promote their organized packing. Loss of the IMAC adhesion molecule Cadherin-related family member 5 (CDHR5) results in significant brush border defects, though the functional properties of this protocadherin have not been thoroughly explored.

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.

The small EF-hand protein CALML4 functions as a critical myosin light chain within the intermicrovillar adhesion complex.

Specialized transporting and sensory epithelial cells employ homologous protocadherin-based adhesion complexes to remodel their apical membrane protrusions into organized functional arrays. Within the intestine, the nutrient-transporting enterocytes utilize the intermicrovillar adhesion complex (IMAC) to assemble their apical microvilli into an ordered brush border. The IMAC bears remarkable homology to the Usher complex, whose disruption results in the sensory disorder type 1 Usher syndrome (USH1).

Increased Risk of CHD in the Presence of rs7865618 (A allele): Tehran Lipid and Glucose Study.

Background: Recent genome-wide association studies (GWAS) in European populations have indicated that the rs12526453 polymorphism located in phosphatase and actin regulator 1 gene (PHACTR1), mapping to chromosome 6p24 and rs7865618 polymorphism in the cyclin-dependent kinase inhibitor B antisense RNA 1 gene (CDKN2B-AS1) on 9p21.3 are associated with coronary heart disease (CHD). This study was carried out to investigate the association of these polymorphisms and CHD in an Iranian population.

Shared molecular networks in orofacial and neural tube development.

Background: Single genetic variants can affect multiple tissues during development. Thus it is possible that disruption of shared gene regulatory networks might underlie syndromic presentations. In this study, we explore this idea through examination of two critical developmental programs that control orofacial and neural tube development and identify shared regulatory factors and networks.