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FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase expressed in hematopoietic cells. Internal-tandem duplication domain (ITD) mutation and tyrosine kinase domain (TKD) mutation are the two most common mutations in acute myeloid leukemia (AML). Post-translational modifications (PTMs) of FLT3, such as glycosylation and ubiquitination, have been shown to impact various aspects of the protein in both wild-type (WT) and mutant forms of FLT3. In this review, we describe how the glycosylation status of FLT3 affects its subcellular localization, which significantly impacts the activation of downstream signaling, and the impact of specific ubiquitination on FLT3 function and stability, which may be associated with disease progression. Moreover, potential novel therapeutic strategies involving a combination of FLT3 tyrosine kinase inhibitors and drugs targeting glycosylation or ubiquitination are discussed.

Preclinical studies on pathological pain rely on the von Frey test to examine changes in mechanical thresholds and the acetone spray test to determine alterations in cold sensitivity in rodents. These tests are typically conducted on rodent hindpaws, where animals with pathological pain show reliable nocifensive responses to von Frey filaments and acetone drops applied to the hindpaws. Pathological pain in orofacial regions is also an important clinical problem and has been investigated with rodents. However, performing the von Frey and acetone spray tests in the orofacial region has been challenging, largely due to the high mobility of the head of testing animals. To solve this problem, we implemented a sheltering tube method to assess orofacial nociception in mice. In experiments, mice were sheltered in elevated tubes, where they were well accommodated because the tubes provided safe shelters for mice. Examiners could reliably apply mechanical stimuli with von Frey filament, cold stimuli with acetone spray, and light stimuli with a laser beam to the orofacial regions. We validated this method in Nav1.8-ChR2 mice treated with oxaliplatin that induced peripheral neuropathy. Using the von Frey test, orofacial response frequencies and nociceptive response scores were significantly increased in Nav1.8-ChR2 mice treated with oxaliplatin. In the acetone spray test, the duration of orofacial responses was significantly prolonged in oxaliplatin-treated mice. The response frequencies to laser light stimulation were significantly increased in Nav1.8-ChR2 mice treated with oxaliplatin. Our sheltering tube method allows us to reliably perform the von Frey, acetone spray, and optogenetic tests in orofacial regions to investigate orofacial pain. [ABSTRACT FROM AUTHOR]

Mechanical stretch of baroreceptors in the wall of the aortic arch and carotid sinus initiates autonomic reflexes to change heart rate and blood pressure for cardiovascular homeostasis. In this issue of the JCI, Lu et al. show that tentonin 3 (TTN3), a recently identified stretch-sensitive ion channel, was present at the vagus afferent nerve endings innervating the aortic arch to function as a baroreceptor. This study expands the molecular profiles of baroreceptors and provides new insights into molecular mechanisms underlying the regulation of cardiovascular functions through baroreceptor function., Baroreceptor reflex Blood pressure (BP), the major determinant of organ perfusion, is tightly regulated by negative feedback systems to ensure homeostasis in the event of cardiovascular stress. For example, gravity, [...]

Understanding basic neuronal mechanisms hold the hope for future treatment of brain disease. The 1st international conference on synapse, memory, drug addiction and pain was held in beautiful downtown Toronto, Canada on August 21-23, 2006. Unlike other traditional conferences, this new meeting focused on three major aims: (1) to promote new and cutting edge research in neuroscience; (2) to encourage international information exchange and scientific collaborations; and (3) to provide a platform for active scientists to discuss new findings. Up to 64 investigators presented their recent discoveries, from basic synaptic mechanisms to genes related to human brain disease. This meeting was in part sponsored by Molecular Pain, together with University of Toronto (Faculty of Medicine, Department of Physiology as well as Center for the Study of Pain). Our goal for this meeting is to promote future active scientific collaborations and improve human health through fundamental basic neuroscience researches. The second international meeting on Neurons and Brain Disease will be held in Toronto (August 29-31, 2007).