HuD distribution changes in response to heat shock but not neurotrophic stimulation.
Cellular stress leads to a change in distribution of RNA-binding proteins. HuR, a member of the ELAV/Hu family of RNA-binding proteins, is nuclear in distribution and following heat shock is found in large cytoplasmic stress granules where translation is inhibited. HuD, another ELAV/Hu RNA-binding protein, stabilizes the GAP-43 mRNA in response to nerve growth factor (NGF) stimulation in PC12 cells. We were interested in determining the nuclear distribution of HuD and if neurotrophic stimulation induced changes in the distribution of HuD. In PC12 cells, we found, as expected, that HuR translocates from the nucleus to the cytoplasm in response to heat shock. In response to heat shock, HuD forms large cytoplasmic stress granules, consistent with a role for HuD in the cessation of translation. In unstimulated cells, HuD is distributed in small granules in the cytoplasm and is consistently present at low levels in the nucleus. Stimulation of PC12 cells with NGF induces neuronal differentiation including outgrowth of neurites and increased levels of GAP-43 protein, whereas HuD remains localized in small cytoplasm granules and is still present in the nucleus. These results suggest that, following neurotrophic stimulation, the lack of changes in HuD distribution are due to continued steady state of HuD nuclear shuttling in PC12 cells, or that HuD is not normally shuttled from the nucleus in response to NGF.
Burry
Richard W
RW
Department of Neuroscience, 4068 Graves Hall, College of Medicine, The Ohio State University, 333 West Tenth Avenue, Columbus, OH, USA. burry.1@osu.edu
Smith
Catherine L
CL
D000818:Animals; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D003594:Cytoplasmic Granules / Q000378:metabolism / Q000648:ultrastructure; D051959:ELAV Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D018869:Heat-Shock Response; D020932:Nerve Growth Factor / Q000494:pharmacology / Q000502:physiology*; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D016716:PC12 Cells; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D051959:ELAV Proteins; D012333:RNA, Messenger; D020932:Nerve Growth Factor