Progressive disorganization of paranodal junctions and compact myelin due to loss of DCC expression by oligodendrocytes.
نویسندگان
چکیده
Paranodal axoglial junctions are critical for maintaining the segregation of axonal domains along myelinated axons; however, the proteins required to organize and maintain this structure are not fully understood. Netrin-1 and its receptor Deleted in Colorectal Cancer (DCC) are proteins enriched at paranodes that are expressed by neurons and oligodendrocytes. To identify the specific function of DCC expressed by oligodendrocytes in vivo, we selectively eliminated DCC from mature myelinating oligodendrocytes using an inducible cre regulated by the proteolipid protein promoter. We demonstrate that DCC deletion results in progressive disruption of the organization of axonal domains, myelin ultrastructure, and myelin protein composition. Conditional DCC knock-out mice develop balance and coordination deficits and exhibit decreased conduction velocity. We conclude that DCC expression by oligodendrocytes is required for the maintenance and stability of myelin in vivo, which is essential for proper signal conduction in the CNS.
منابع مشابه
Maintenance of axo-oligodendroglial paranodal junctions requires DCC and netrin-1.
Paranodal axoglial junctions are essential for the segregation of myelinated axons into distinct domains and efficient conduction of action potentials. Here, we show that netrin-1 and deleted in colorectal cancer (DCC) are enriched at the paranode in CNS myelin. We then address whether netrin-1 signaling influences paranodal adhesion between oligodendrocytes and axons. In the absence of netrin-...
متن کاملNovel Molecular Mechanisms of Neuronal and Vascular Protection in Experimental Glaucoma
Paranodal axoglial junctions are essential for the segregation of myelinated axonsinto distinct domains and efficient conduction of action potentials. Here, we show thatnetrin-1 and deleted in colorectal cancer (DCC) are enriched at the paranode in CNSmyelin. We then address whether netrin-1 signaling influences paranodal adhesionbetween oligodendrocytes and axons. In the absenc...
متن کاملContactin-1 regulates myelination and nodal/paranodal domain organization in the central nervous system.
Myelin, a multilayered membrane sheath formed by oligodendrocytes around axons in the CNS, enables rapid nerve impulse conduction and sustains neuronal health. The signals exchanged between axons and oligodendrocytes in myelin remain to be fully elucidated. Here we provide genetic evidence for multiple and critical functions of Contactin-1 in central myelin. We document dynamic Contactin-1 expr...
متن کاملDependence of nodal sodium channel clustering on paranodal axoglial contact in the developing CNS.
Na(+) channel clustering at nodes of Ranvier in the developing rat optic nerve was analyzed to determine mechanisms of localization, including the possible requirement for glial contact in vivo. Immunofluorescence labeling for myelin-associated glycoprotein and for the protein Caspr, a component of axoglial junctions, indicated that oligodendrocytes were present, and paranodal structures formed...
متن کاملChanges in the expression and localization of the paranodal protein Caspr on axons in chronic multiple sclerosis.
The presence of intact paranodal junctions on myelinated axons in the CNS and PNS is crucial for both myelin sheath attachment and saltatory impulse conduction. The axonal glycoprotein contactin-associated protein (Caspr) is expressed in the paranodal region and plays an important role in the creation and maintenance of these adhesive junctions. In the present study, antibodies to Caspr were us...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- The Journal of neuroscience : the official journal of the Society for Neuroscience
دوره 34 29 شماره
صفحات -
تاریخ انتشار 2014