ATP Enhances Neuronal Differentiation of PC12 Cells by Activating PKC alpha Interactions with Cytoskeletal Proteins

• PKC alpha is a key mediator of the neuronal differentiation controlled by NGF and ATP. However, its down stream signaling pathways remain to be elucidated. To identify the signaling partners of PKC alpha, we analyzed proteins coimmunoprecipitated with this enzyme in PC12 cells differentiated with NGF and ATP and compared them with those obtained with NGF alone or growing media. Mass spectrometry analysis (LC-MS/MS) identified plectin, peripherin, filamin A, fascin, and beta-actin as potential interacting proteins. The colocalization of PKC alpha and its interacting proteins increased when PC12 cells were differentiated with NGF and ATP. Peripherin and plectin organization and the cortical remodeling of beta-actin were dramatically affected when PKC alpha was down-regulated, suggesting that all three proteins might be functional targets of ATP-dependent PKC alpha signaling. Taken together, these data demonstrate that PKC alpha is essential for controlling the neuronal development induced by NGF and ATP and interacts with the cytoskeletal components at two levels: assembly of the intermediate filament peripherin and organization of cortical actin.

Ämnesord

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Nyckelord

cytoskeleton

proteomics

PKC

plectin

peripherin

ATP receptors

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