Developmental changes in expression of myotonic dystrophy protein kinase in the rat central nervous system

Abstract

Myotonic dystrophy protein kinase (DMPK) is the protein product of the genetic locus associated with myotonic dystrophy, in which alterations of muscle excitability, cardiac conduction defects, mental retardation, and cognitive deficiencies are inherited as an autosomal dominant trait. DMPK belongs to a novel protein serine/threonine kinase family, but its regulation and physiological functions have not been specified. In a first step toward understanding the functions of DMPK in the central nervous system, we have characterized its localization and developmental pattern of expression in rat brain and spinal cord by using a monospecific rabbit antiserum produced against bacterially expressed DMPK. Expression of DMPK begins after birth and increases gradually to peak at postnatal day 21 with antibody labeling of neuronal cell types in many regions. After postnatal day 21 and proceeding to the adult, the pattern of expression becomes more restricted, with localization to certain regions or cell groups in the central nervous system. Electron microscopy reveals localization within adult spinal motor neurons to the endoplasmic reticulum and dendritic microtubules. The adult localizations suggest that DMPK may function in membrane trafficking and secretion within neurons associated with cognition, memory, and motor control.

Cognitive impairment in neuromuscular disorders

“…In the central nervous system, DMPK is synaptically localized in the cerebellum, midbrain, hippocampus, and medulla, at the apical membrane of the ependyma and choroid plexus, and postsynaptically at the neuromuscular junction of skeletal muscle, and the intercalated disks of cardiac tissue 220. DMPK expression in rat brain and spinal cord begins after birth and increases gradually to adulthood, with a localization within adult spinal motor neurons to the endoplasmic reticulum and dendritic microtubules, suggesting a role in membrane trafficking and secretion within neurons associated with cognition, memory, and motor control 13…”

Myotonic Dystrophy Protein Kinase: Structure, Function and Its Possible Role in the Pathogenesis of Myotonic Dystrophy Type 1

“…The analysis revealed a shift in the DMPK subcellular localization during myogenesis, from the perinuclear region to the cellular membrane, suggesting the possibility that DMPK performs different roles during this process (Reddy et al, 1996). Electron microscopy analyses in adult rat spinal motor neurons reveal a localization of DMPK in the endoplasmic reticulum and dendritic microtubules, suggesting a function in membrane trafficking and secretion within neurons associated with cognition, memory, and motor control (Balasubramanyam et al, 1998). In addition, multiple subcellular localizations have been assigned to DMPK, including neuromuscular and myotendinous junctions Berul et al, 2000;Shimokawa et al, 1997) and terminal cisternae and intercalated discs of skeletal muscle sarcoplasmic reticulum (Benders et al, 1997;Pall et al, 2003;Saba et al, 1999).…”

“…In brain and spinal cord of rat, DMPK begins to be expressed after birth and increases gradually to peak at postnatal day 21 in many regions. After that and proceeding to the adult stage, DMPK expression becomes more restricted to certain cell groups like spinal motor neurons (Balasubramanyam et al, 1998). Immunoreactive neurons have been observed in the early fetal frontal cortex and cerebellar granule cell layer before 29 weeks of gestation (Endo et al, 2000).…”

“…DMPK is expressed in a subpopulation of neurons associated with cognition, memory, and motor control. It is localized in the endoplasmic reticulum and dendritic microtubules within adult spinal motor neurons (Balasubramanyam et al, 1998). DMPK has been also associated with intracellular communication functions, due to its synaptic localization in cerebellum, hippocampus, midbrain and medulla (Whiting et al, 1995).…”

Advances in Protein Kinases

“…In brain and spinal cord of rat, DMPK begins to be expressed after birth and increases gradually to peak at postnatal day 21 in many regions. After that and proceeding to the adult stage, DMPK expression becomes more restricted to certain cell groups like spinal motor neurons (Balasubramanyam et al, 1998). Immunoreactive neurons have been observed in the early fetal frontal cortex and cerebellar granule cell layer before 29 weeks of gestation (Endo et al, 2000).…”