Fam134c and C3orf10 Differentially Involved in Axonal and Dendritic Growth of Rat Hippocampal Neurons under Different Rigidity of Matrix

摘要

Neurite outgrowth is a critical process of neuronal differentiation In addition to chemical factors physical factors such as mechanical forces imposed by the environment are important to neuronal development Mechanical properties of extracellular environment have been implicated in differentiation of neuronal stem cells and maturation of neurons However which genes are involved in mechanobiology of neurite outgrowth remains largely unknown Previous studies indicated that two novel genes family with sequence similarity 134 member C (Fam134c) and chromosome 3 open reading frame 10 (C3orf10) differentially regulate axonal and dendritic growth in rat hippocampal neurons Fam134c is predicted as a membrane protein and C3orf10 is proposed to involve actin nucleation Focal adhesion kinase (FAK) is key molecule in mechanosensitivity in non-neuronal cells We hypothesized that Fam134c and C3orf10 involved in mechanbiology of neurite outgrowth under different rigidity of matrix and are up- or down-stream signaling molecules of FAK RNA interference was used to knockdown Fam134c or C3orf10 of cultured rat hippocampal neurons on different rigidity of polyacrylamide gel and glass dish Immunocytochemistry was used to observe neuronal morphology and detect protein distribution Primary rat hippocampal neurons exhibit the rigidity-dependent increases in the length of axons However knockdown of Fam134c decreases the length of axons on glass dish but increases the length of axons on soft gel In contrast knockdown of C3orf10 increases the length of primary dendrites on rigid matrix Immunointensity of both Fam134c and C3orf10 in cell bodies showed rigidity-dependent decrease However immunointensity of Fam134c in axons increases on soft gel but that of C3orf10 has no difference on different rigidity Immunointensity of phosphorylated FAK (pFAK) exhibits rigidity-dependent increases in primary rat hippocampal neurons Fam134c and C3orf10 colocalize with pFAK and paxillin on different rigidity of matrix Knockdown of C3orf10 decreases the expression of pFAK on rigid matrix but not on soft matrix These results suggest that Fam134c and C3orf10 differentially modulate axonal and dendritic growth and involve in mechanosensing through the interaction with FAK Delineation of underlying mechanisms of Fam134c and C3orf10 in mechanobiology of neurons will provide important knowledge how neurons of central nervous system sense the rigidity of extracellular matrix

獎項日期	2014 8月 26
原文	English
監督員	A-Min Huang (Supervisor)