The Role Of PAK1 Gene In Hearing Loss

Hearing loss is a very common disease in clinic.It can be divided into two groups: syndromic deafness and non-syndromic deafness.It has been reported that the rate of autism in deafness children is much higher than in normal children.Autism is a pervasive and complex developmental disorder that is characterised by having difficulties in the areas of social interaction,communication and restricted and repetitive behaviour.Several clinical paper reveal that the rate of autism in hearing loss children is higher then in normal children.However,by far only very few genes have been identified to clearly related with both autism and deafness.The autism related gene PAK1(p21-activated kinase 1)is a serine/threonine kinase,which plays important roles in a variety of cellular processes,including cytoskeleton dynamics,cell migration,cell polarization,cell cycle progression,and apoptosis.As an autism-related protein,PAK1 regulates synapse formation and plasticity by affecting polymerization of actin filaments in neuron.Actin-based cytoskeleton also plays critical roles in morphogenesis of sensory hair cells(HCs),especially in the development of hair bundles.However,the role of PAK1 in hearing has not been investigated yet.In this research,we first found PAK1 extensively expressed in the HCs of mice cochlea.Then,we explored the function of PAK1 in hearing using the Pak1-/-mice.The ABR and DPOAE data showed that PAK1 disruption indeed induced hearing impairment.Thirdly,we found that the HC survival,synapse density,and hair bundle morphogenesis were all affected in Pak1-/-mice.Further investigations revealed that PAK1 disruption significantly reduced the level of p-ERM and p-cofilin in mice cochlea,which might be the reasons for that abnormalities in Pak1-/-mice.Taken together,we identified a novel gene PAK1 involved in both autism and hearing impairment.