LRRC10
Leucine-rich repeat containing protein (LRRC)10 is a cardiac-specific member of the LRRC superfamily.
Contents
Action
LRRC10 has no other known functional domains other than its LRRs (28 in [1]), suggesting that it mediates its biological functions by interacting with other proteins.
LRRC10 interacts with actin and α-actinin in the heart (8) and localizes at the dyad region where the Z-disc comes into close juxtaposition to the T-tubule and sarcoplasmic reticulum (8, 28).
This places LRRC10 at a mechanosensitive signaling hub in cardiomyocytes (19).
Lrrc10−/− mice exhibit increased cardiac growth in response to pressure overload [1].
Lrrc10−/− myocytes have reduced single cell contractility in response to adrenergic stimulation, indicating that LRRC10 is indispensable for the response of the mammalian heart to biomechanical stress [1].
Deletion of Lrrc10 greatly exacerbates cardiac dysfunction in response to pressure overload [1].
His150 of LRRC10 mediates its interaction with actin in the heart and that the interaction of LRRC10 with actin is reduced after pressure overload, suggesting a potential mechanosensing function for LRRC10 [1].
LRRC10 may serve as a cardiomyocyte-specific scaffolding protein to tether important structural or signaling molecules to mediate appropriate responses to mechanical stress. Z-disc proteins such as muscle LIM protein (2, 29), Cypher (56, 57), and telethonin (29, 30) are thought to compose a mechanosensory signalosome that allows the cardiomyocyte to internally sense and respond to mechanical stretch or strain [1].
Moreover, LRRC39, a striated muscle-specific LRRC, acts as a mechanosensor at the cardiomyocyte M-line by regulating serum response factor-dependent transcription (51).
Pathways
The cardiomyocyte-specific expression of Lrrc10 is regulated by Nkx2.5, GATA4, and serum response factor (7).
Diseases
Mutations in the LRRC10 gene have been recently linked to human dilated cardiomyopathy (43).
Expression
Lrrc10 is expressed exclusively in cardiomyocytes [1].
