The Non-Canonical Wnt/PKC Pathway Regulates Mitochondrial Dynamics through Degradation of the Arm-Like Domain-Containing Protein Alex3

The regulation of mitochondrial dynamics is vital in complex cell types, such as neurons, that transport and localize mitochondria in high energy-demanding cell domains. The Armcx3 gene encodes a mitochondrial-targeted protein (Alex3) that contains several arm-like domains. In a previous study we showed that Alex3 protein regulates mitochondrial aggregation and trafficking. Here we studied the contribution of Wnt proteins to the mitochondrial aggregation and dynamics regulated by Alex3. Overexpression of Alex3 in HEK293 cells caused a marked aggregation of mitochondria, which was attenuated by treatment with several Wnts. We also found that this decrease was caused by Alex3 degradation induced by Wnts. While the Wnt canonical pathway did not alter the pattern of mitochondrial aggregation induced by Alex3, we observed that the Wnt/PKC non-canonical pathway regulated both mitochondrial aggregation and Alex3 protein levels, thereby rendering a mitochondrial phenotype and distribution similar to control patterns. Our data suggest that the Wnt pathway regulates mitochondrial distribution and dynamics through Alex3 protein degradation

Podocalyxin Is a Novel Polysialylated Neural Adhesion Protein with Multiple Roles in Neural Development and Synapse Formation

Neural development and plasticity are regulated by neural adhesion proteins, including the polysialylated form of NCAM (PSA-NCAM). Podocalyxin (PC) is a renal PSA-containing protein that has been reported to function as an anti-adhesin in kidney podocytes. Here we show that PC is widely expressed in neurons during neural development. Neural PC interacts with the ERM protein family, and with NHERF1/2 and RhoA/G. Experiments in vitro and phenotypic analyses of podxl-deficient mice indicate that PC is involved in neurite growth, branching and axonal fasciculation, and that PC loss-offunction reduces the number of synapses in the CNS and in the neuromuscular system. We also show that whereas some of the brain PC functions require PSA, others depend on PC per se. Our results show that PC, the second highly sialylated neural adhesion protein, plays multiple roles in neural development

Anatomía arterial de los colgajos musculares de extensor carpi radialis longus y extensor carpi radialis brevis para su uso en transferencia muscular funcional libre Arterial anatomy of the extensor carpi radialis longus and extensor carpi radialis brevis muscle flaps related to its use in free functioning muscle transfer

El objetivo de este trabajo es documentar el aporte arterial y el patrón vascular intramuscular de los músculos Extensor Carpi Radialis Longus (ECRL) y Extensor Carpi Radialis Brevis (ECRB) para analizar su utilización como colgajos libres en transferencia muscular funcional para reanimación facial. Realizamos un estudio anatómico en 29 brazos humanos en fresco. Las técnicas de inyección utilizadas fueron la modificada de oxido de plomo y gelatina en 11 cadáveres y la de inyección pulsátil de látex color en 18. Disecamos los músculos ECRL y ECRB y sus pedículos, los fotodocumentamos y radiografiamos valorando los resultados en función del patrón vascular intramuscular, relaciones anatómicas, calibres y longitud de pedículos. Encontramos dos patrones vasculares diferentes en las 29 disecciones siguiendo la clasificación de Mathes y Nahai de la anatomía vascular de los músculos (en función del número de pedículos vasculares y su dominancia): Tipo I( 37,9% ECRL y 20,7% ECRB) y Tipo II(62,1% del ECRL y 79,3% del ECRB). El pedículo principal del ECRL (de diámetro medio 1,73 mm y longitud de pedículo media de 32,32 mm) es en el 100% de los casos rama de la arteria recurrente radial y el pedículo principal del ECRB (de diámetro medio 1,11 mm y longitud de pedículo media de 27,77 mm) es rama de la arteria radial en el 68,9% de los casos y de la arteria recurrente radial en el 31,1% de los casos. Concluimos que El ECRL y ECRB presentan dos tipos de patrones vasculares: tipo I y tipo II, siendo más frecuente en nuestro trabajo el tipo II, que hacen que ambos puedan ser transferidos como colgajos libres por su pedículo principal. Ambos músculos presentan un tamaño, contorno, contenido fascial importante para el anclaje de suturas y una longitud de pedículo y calibre vascular adecuados para su transferencia microvascular libre en reanimación facial. De los dos, el más realizable como colgajo libre es el ECRB ya que la relación anatómica del nervio radial con el pedículo del ECRL hace que no sea posible su transferencia como colgajo libre sin sacrificar la rama motora del nervio radial en la mayor parte de los casos.<br>The arterial anatomy of the Extensor Carpi Radialis Longus and Brevis (ECRL, ECRB) flaps is herein described in order to provide the vascular basis to be used as free muscle transfer for facial reanimation. We used 29 fresh above-elbow human arms injected by means of two diferent techniques.Latex-injection was performed in 18 arms and the modified lead oxide-gelatine injection technique was performed in 11 arms. The ECRL and ECRB with their pedicles were dissected, photodocumented and radiographied.The number, length and calibers of the muscle pedicles were recorded. The intramuscular vascular pattern and the relations of the main pedicles of the muscles with the radial nerve were also noted. Two vascular patterns were found following the Mathes and Nahai Classification of the Vascular Anatomy of the Muscles (number of pedicles and its dominance): Type I (37,9% of ECRL and 20,7% of ECRB dissections) and Type II (62,1% of ECRL and 79,3% of ECRB dissections). The dominant pedicle for the ECRL (with an average caliber of 1,73 mm and an average length of pedicle of 32,32 mm) is a branch of the radial recurrent artery in 100% of the dissections and the dominant pedicle for the ECRB (with an average caliber of 1,11 mm and an average length of pedicle of 27,77 mm) a branch of the radial artery in 68,9% of the dissections and a branch of radial recurrent artery in 31,1% of the cases. As a conclusion, ECRL and ECRB muscle flaps present two types of vascular patterns: type I and type II.Type II pattern is the most common in our study. The anatomical features of both muscles (vascular basis,presence of an important fascial layer, contour and length of the muscle,) make them reliable as free muscles flaps for facial reanimation, however, the relation between the dominant pedicle for the ECRL muscle flap with the posterior interosseous branch of the radial nerve make not possible to free the flap without sacrificing the nerve in most of the cases

Peroneal tendons well vascularized: results from a cadaveric study

Peroneal tendon tears are relatively common injuries that seem to have a poor healing tendency. The discussion goes that peroneal tendons have avascular zones, contributing to the poor healing of those tears. The purpose of this study was to provide evidence on the vascularization pattern of the peroneal tendons. Methods: Ten adult fresh-frozen cadavers were obtained from a university-affiliated body donation programme. The femoral artery was injected with natural coloured latex at the level of the knee. Macroscopic and microscopic dissections were performed to visualize the vascularization towards the peroneal tendons. To expose intratendinous vascularity, the tendons were cleared using a modified Spälteholz technique. Results: In all specimens, blood was mainly supplied by the peroneal artery through a posterolateral vincula connecting both tendons. Branches were bifurcated every 3.9 ± 1.8 cm, starting 24 ± 5.3 cm proximal to the tip of the fibula. Eight out of 10 (80 %) specimens had poor vascularized zones in the peroneus longus tendon. No avascular zones were found in the peroneus brevis tendon. Conclusion: The peroneal tendons are well vascularized by the peroneal artery, via vessels running through a common vincula for both tendons. In the peroneus brevis, no avascular zones were found. To keep the tendons well vascularized and therefore improve tendon healing, surgeons should be careful leaving the vincula intact during surgical procedure

Reelin expression and glycosylation patterns are altered in Alzheimer’s disease

Reelin is a glycoprotein that is essential for the correct cytoarchitectonic organization of the developing CNS. Its function in the adult brain is less understood, although it has been proposed that Reelin is involved in signaling pathways linked to neurodegeneration. Here we analyzed Reelin expression in brains and cerebrospinal fluid (CSF) from Alzheimer’s disease (AD) patients and nondemented controls. We found a 40% increase in the Reelin protein levels in the cortex of AD patients compared with controls. Similar increases were detected at the Reelin mRNA transcriptional level. This expression correlates with parallel increases in CSF but not in plasma samples. Next, we examined whether CSF Reelin levels were also altered in neurological diseases, including frontotemporal dementia, progressive supranuclear palsy, and Parkinson’s disease. The Reelin 180-kDa band increased in all of the neurodegenerative disorders analyzed. Moreover, the 180-kDa Reelin levels correlated positively with Tau protein in CSF. Finally, we studied the pattern of Reelin glycosylation by using several lectins and the anti-HNK-1 antibody. Glycosylation differed in plasma and CSF. Furthermore, the pattern of Reelin lectin binding differed between the CSF of controls and in AD. Our results show that Reelin is up-regulated in the brain and CSF in several neurodegenerative diseases and that CSF and plasma Reelin have distinct cellular origins, thereby supporting that Reelin is involved in the pathogenesis of a number of neurodegenerative diseases