Rabbit Anti-Human RAC1 (a.a. 1-192) Polyclonal antibody

FAM46C, frequently mutated in multiple myeloma (MM), has recently been shown to encode a non-canonical poly(A) polymerase (ncPAP). However, its target mRNAs and its role in MM pathogenesis remain mostly unknown. Using CRISPR-Cas9 technology and gene expression analysis, we found that the inactivation of FAM46C in MM down-regulates immunoglobulins (Igs) and several mRNAs encoding ER-resident proteins, including some involved in unfolded protein response and others that affect glycosylation. Interestingly, we show that FAM46C expression is induced during plasma cell (PC) differentiation and that Ig mRNAs encoding heavy and light chains are substrates of the ncPAP, as revealed by poly(A) tail-length determination assays. The absence of the ncPAP results in Ig mRNA poly( A) tail-shortening, leading to a reduction in mRNA and protein abundance. On the other hand, loss of FAM46C upregulates metastasis-associated lncRNA MALAT1 and results in a sharp increase in the migration ability. This phenotype depends mainly on the activation of PI3K/Rac1 signalling, which might have significant therapeutic implications. In conclusion, our results identify Ig mRNAs as targets of FAM46C, reveal an important function of this protein during PC maturation to increase antibody production and suggest that its role as a tumour suppressor might be related to the inhibition of myeloma cell migration.

Excitatory synapse formation begins in mid-fetal gestation. However, due to our inability to image fetal synaptogenesis, the initial formation of synapses remains understudied. The recent development of human fetal brain spheroids provides access to this critical period of synapse formation. Using human neurons and brain spheroids, we address how altered actin regulation impacts the formation of excitatory synapses during fetal brain development. Prior to synapse formation, inhibition of RhoA kinase (ROCK) signaling promotes neurite elongation and branching. In addition to increasing neural complexity, ROCK inhibition increases the length of protrusions along the neurite, ultimately promoting excitatory synapse formation in human cortical brain spheroids. A corresponding increase in Rac1-driven actin polymerization drives this increase in excitatory synaptogenesis. Using STORM super-resolution microscopy, we demonstrate that actomyosin regulators, including the Rac1 regulator, alpha-PIX, and the RhoA regulator, p115-RhoGEF, localize to nascent excitatory synapses, where they preferentially localize to postsynaptic compartments. These results demonstrate that coordinated RhoGTPase activities underlie the initial formation of excitatory synapses and identify critical cytoskeletal regulators of early synaptogenic events.