Golgi Complex, Endoplasmic Reticulum Exit Sites, and Microtubules in Skeletal Muscle Fibers Are Organized by Patterned Activity

Abstract

The Golgi complex of skeletal muscle fibers is made of thousands of dispersed elements. The distributions of these elements and of the microtubules they associate with differ in fast compared with slow and in innervated compared with denervated fibers. To investigate the role of muscle impulse activity, we denervated fast extensor digitorum longus (EDL) and slow soleus (SOL) muscles of adult rats and stimulated them directly with patterns that resemble the impulse patterns of normal fast EDL (25 pulses at 150 Hz every 15 min) and slow SOL (200 pulses at 20 Hz every 30 sec) motor units. After 2 weeks of denervation plus stimulation, peripheral and central regions of muscle fibers were examined by immunofluorescence microscopy with regard to density and distribution of Golgi complex, microtubules, glucose transporter GLUT4, centrosomes, and endoplasmic reticulum exit sites. In extrajunctional regions, fast pattern stimulation preserved normal fast characteristics of all markers in EDL type IIB/IIX fibers, although inducing changes toward the fast phenotype in originally slow type I SOL fibers, such as a 1.5-fold decrease of the density of Golgi elements at the fiber surface. Slow pattern stimulation had converse effects such as a 2.2-fold increase of the density of Golgi elements at the EDL fiber surface. In junctional regions, where fast and slow fibers are similar, both stimulation patterns prevented a denervation-induced accumulation of GLUT4. The results indicate that patterns of muscle impulse activity, as normally imposed by motor neurons, play a major role in regulating the organization of Golgi complex and related proteins in the extrajunctional region of muscle fibers.

Microtubule binding distinguishes dystrophin from utrophin

“…Additionally, it is known that vesicular trafficking and organelle localization require proper microtubule function in muscle cells (20,54). Despite these insights into microtubule function, little is known about the relevance of microtubule tethering and lattice organization in skeletal muscle.…”

Muscle plasticity related to changes in tubulin and αB-crystallin levels induced by eccentric contraction in rat skeletal muscles

“…As an unexpected novel finding of this study, this difference suggests that different levels of electrical stimulation might be an important factor for controlling the expression of tubulin and that α-tubulin is potentially controlled by neuronal stimulation. Ralston et al (29) reported that different frequencies of electrical stimulation induced different densities and orientations of microtubules in the soleus (which dominantly has MHC I) and extensor digitorum longus (which dominantly has MHC II) muscles, whereby 150 Hz (100 Hz in this study) stimulation applied to the fast muscle preserved the pattern/quantity of microtubules; however, microtubules in the slow muscle under the same stimulation showed thinner and were fewer in quantity. We have hypothesized that a decrease in the pool of tubulin dimers rather than a decrease in microtubules is caused by higher frequencies of electrical stimulation comparing with the lower ones.…”

“…For MHC isoforms in slow and fast muscles, their isoform transitions show the following order MHC I↔MHC IIa↔MHC IId/x↔MHC IIb (9). Ralston et al (29) reported that 20 Hz stimulation induced a slow type I pattern in extensor digitorum longus fibers (fast) muscle, but stimulation with 150 Hz only partially succeeded in inducing a type II pattern in the soleus (slow) muscle. The difference in frequency of electrical stimulation (100 Hz of EIEC used in this study and 150 Hz of EIEC used in Ralston et al's study) might be responsible for the different results in this study compared with those of Ralston et al (29).…”

“…These results may be caused by a number of mechanisms. Different degrees of electrical stimulation to the skeletal muscles could cause variations in the quantity of tubulin per microtubule (29). The active and direct electrical stimulation of the GCM sustains tubulin levels.…”

“…Microtubules, which consist of tubulin, are associated with different fibril types depending on muscle fibers and their protein contents, and their plasticity is controlled by electrical activity (29). We previously traced these proteins to determine whether the system formed by αB-crystallin and its substrate (tubulin) responds to mechanical environmental demands resulting in morphological and biochemical responses, which lead to adaptive transformation of the skeletal muscle (13,15).…”