Key result
POPDC loss-of-function mutations are linked to sick sinus syndrome, AV block, and muscular dystrophy.
Why the study?
POPDC proteins act as cAMP effector proteins involved in cAMP signaling, but their exact biochemical activity is poorly understood.
Understanding the function of POPDC proteins highlights a novel mechanism of cAMP signaling compartmentalization essential for normal cardiac pacemaking and conduction.
No immediate practice change; leaves open POPDC-targeted research on cAMP compartmentalization in conduction disorders.
, encodes transmembrane proteins abundantly expressed in striated muscle. POPDC proteins have recently been identified as cAMP effector proteins and have been proposed to be part of the protein network involved in cAMP signaling. However, their exact biochemical activity is presently poorly understood. Loss-of-function mutations in animal models causes abnormalities in skeletal muscle regeneration, conduction, and heart rate adaptation after stress. Likewise, patients carrying missense or nonsense mutations in POPDC genes have been associated with cardiac arrhythmias and limb-girdle muscular dystrophy. In this review, we introduce the POPDC protein family, and describe their structure function, and role in cAMP signaling. Furthermore, the pathological phenotypes observed in zebrafish and mouse models and the clinical and molecular pathologies in patients carrying POPDC mutations are described.
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Gruscheski et al. (2021) conducted a review in Cardiac arrhythmias and limb-girdle muscular dystrophy. POPDC gene mutations was evaluated. Loss-of-function mutations in POPDC genes disrupt cAMP signaling and are associated with cardiac arrhythmias, such as sick sinus syndrome and AV block, as well as limb-girdle muscular dystrophy.
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