All of the following steps are critical for retrograde transport of BDNF survival signals into the nucleus in neurons EXCEPT

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The question asks us to identify which step is NOT critical for retrograde transport of BDNF survival signals into the nucleus in neurons, but the provided data is incomplete because no full list of answer options is present. We can still reason about the likely nature of such steps and evaluate the single listed option in that context.

Option provided for analysis: 'Binding of BDNF to presynaptic Trk-B receptors activates serine phosphorylation.'

First, consider how BDNF signaling typically initiates. BDNF binds to TrkB receptors, which leading to receptor dimerization and activation primarily through tyrosine autophosphorylation of the TrkB cytoplasmic domain. This tyrosine phosphorylation creates docking sites for signaling cascades (e.g., MAPK/ERK, PI3K/Akt) that promote survival and plasticity. Serine phosphorylation of TrkB or downstream proteins can occur as a downstream modification, but the hallmark early activation event is tyrosine phosphorylation rather than serine phosphorylation.

Moreover, retrograde signaling involves endocytosis of the BDNF-TrkB complex into signaling endosomes, dynein-mediated transport along microtubules toward the soma, and ultimately activation of transcriptional programs in the nucleus (for example via CREB). Key steps include endocytosis of the activated receptor, proper trafficking of the signaling endosome, retention of signaling during transport, and delivery of signals to the nucleus to induce gene expression for survival.

Given this framework, the statement that the initiating event is 'Binding of BDNF to presynaptic Trk-B receptors activates serine phosphorylation' is at odds with the canonical mechanism. The critical early activation is phosphorylation on tyrosine residues of TrkB, not primarily serine phosphorylation. Therefore, as a statement describing an initiating event, it is inaccurate with respect to the well-established mechanism and would not be considered a critical step in the retrograde signaling process.

If other answer choices were available, we would compare each against the established sequence (BDNF binding → TrkB tyrosine phosphorylation → endocytosis of signaling endosome → dynein-based transport → nuclear signaling). In this scenario, the provided option conflicts with the core mechanistic detail (tyrosine rather than serine phosphorylation), suggesting it is not part of the correct retrograde signaling chain.

In summary, the reasoning supports that the option stating 'Binding of BDNF to presynaptic Trk-B receptors activates serine phosphorylation' is not aligned with the canonical mechanism of initiating TrkB signaling and retrograde transport, and thus would be the EXCEPT if we must pick a non-critical or incorrect step from the set. The absence of the other choices prevents a complete comparative analysis, but the identified logic explains why this particular option is biologically inaccurate as a critical step in the described pathway.

01:146:447:01 CLINICAL NEUROBIO CN F25 Exam 2

All of the following steps are critical for retrograde transport of BDNF survival signals into the nucleus in neurons EXCEPT

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