“Serious irregularities” in Western blots lead to retraction of brain chemistry paper

jneuroscijuly13The Journal of Neuroscience has retracted a 2009 article by a group from Mount Sinai (now the Icahn School of Medicine at Mount Sinai) for suspicious Western blots.

The paper, “Requirement for Protein Synthesis at Developing Synapses,” came from the lab of Deanna Benson, a Parkinson’s expert. According to the abstract, which is still available on the journal’s website:

Activity and protein synthesis act cooperatively to generate persistent changes in synaptic responses. This forms the basis for enduring memory in adults. Activity also shapes neural circuits developmentally, but whether protein synthesis plays a congruent function in this process is poorly understood. Here, we show that brief periods of global or local protein synthesis inhibition decrease the synaptic vesicles available for fusion and increase synapse elimination. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a critical target; its levels are controlled by rapid turnover, and blocking its activity or knocking it down recapitulates the effects of protein synthesis inhibition. Mature presynaptic terminals show decreased sensitivity to protein synthesis inhibition, and resistance coincides with a developmental switch in regulation from CaMKII to PKA (protein kinase A). These findings demonstrate a novel mechanism regulating presynaptic activity and synapse elimination during development, and suggest that protein translation acts coordinately with activity to selectively stabilize appropriate synaptic interactions.

But as the retraction notice states:

The article “Requirement for Protein Synthesis at Developing Synapses” by Joseph Sebeo, Kuangfu Hsiao, Ozlem Bozdagi, Dani Dumitriu, Yongchao Ge, Qiang Zhou, and Deanna L. Benson, which appeared on pages 9778–9793 of the August 5, 2009 issue has been retracted by the authors, who report the following: “It has come to our attention that there were serious irregularities with some of the Western blots in the paper. All authors concur the paper should be retracted to avoid misleading readers and investigators in the field, but we would like to emphasize that the primary effects of protein synthesis blockers on synapses that were described are not in question and will be submitted for publication at a future date. We apologize for any inconvenience or misunderstanding that this may have caused our colleagues.”

The study has been cited 18 times, according to Thomson Scientific’s Web of Knowledge.

We spoke briefly with Benson, who said she couldn’t discuss the case. But she did tell us that she was not expecting any other retractions stemming from whatever went wrong here.

Christie Corbett, a Mount Sinai spokesperson, said the institution could not discuss the case at this time.

0 thoughts on ““Serious irregularities” in Western blots lead to retraction of brain chemistry paper”

  1. The problematic western blots are in Fig. 6 (a-d) on p. 9786:

    These blots, supposedly showing different proteins, are the exact same blots (with slightly different exposures):
    – p-site-3 syn, CAMKII & pCAMKII
    – p-site-1 syn & CAMKI
    – synapsin & tubulin

    This is 7 out of a total of 8 Western blots in the entire paper. And almost all of them are right above or below each other.

      1. Or perhaps the PI. Blaming reviewers is one thing, but to let this slip may prove that this PI does not critically analyze the work that both comes out of her lab and also has her name on it.

  2. This figure from the same group in 2005
    “A Prohormone Convertase Cleavage Site within a Predicted α-Helix Mediates Sorting of the Neuronal and Endocrine Polypeptide VGF into the Regulated Secretory Pathway” JBC

    Considerable amount of splicing.

    Other w-blots are too poor quality to be able to detect splicing/differing exposure if it was present. For example: “Cadherin-8 and N-cadherin Differentially Regulate Pre- and Postsynaptic Development of the Hippocampal Mossy Fiber Pathway”

    1. Where there is splicing there is smoke!

      Good to see the paper retracted, but it would be even better to see why it was retracted, officially.

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