Repair of traumatic plasmalemmal damage to neurons and other eukaryotic cells  

作　　者：George D.Bittner Christopher S.Spaeth Andrew D.Poon Zachary S.Burgess Christopher H.Mc Gill 

机构地区：[1]Department of Neuroscience,The University of Texas at Austin

出　　处：《Neural Regeneration Research》2016年第7期1033-1042,共10页中国神经再生研究（英文版）

基　　金：supported by grants from the Lone Star Paralysis Foundation to GDB and by an NIH grant R01 NS081063 to GDB

摘　　要：The repair（sealing） of plasmalemmal damage,consisting of small holes to complete transections,is critical for cell survival,especially for neurons that rarely regenerate cell bodies.We first describe and evaluate different measures of cell sealing.Some measures,including morphological/ultra-structural observations,membrane potential,and input resistance,provide very ambiguous assessments of plasmalemmal sealing.In contrast,measures of ionic current flow and dye barriers can,if appropriately used,provide more accurate assessments.We describe the effects of various substances（calcium,calpains,cytoskeletal proteins,ESCRT proteins,m UNC-13,NSF,PEG） and biochemical pathways（PKA,PKC,PLC,Epac,cytosolic oxidation） on plasmalemmal sealing probability,and suggest that substances,pathways,and cellular events associated with plasmalemmal sealing have undergone a very conservative evolution.During sealing,calcium ion influx mobilizes vesicles and other membranous structures（lysosomes,mitochondria,etc.） in a continuous fashion to form a vesicular plug that gradually restricts diffusion of increasingly smaller molecules and ions over a period of seconds to minutes.Furthermore,we find no direct evidence that sealing occurs through the collapse and fusion of severed plasmalemmal leaflets,or in a single step involving the fusion of one large wound vesicle with the nearby,undamaged plasmalemma.We describe how increases in perikaryal calcium levels following axonal transection account for observations that cell body survival decreases the closer an axon is transected to the perikaryon.Finally,we speculate on relationships between plasmalemmal sealing,Wallerian degeneration,and the ability of polyethylene glycol（PEG） to seal cell membranes and rejoin severed axonal ends – an important consideration for the future treatment of trauma to peripheral nerves.A better knowledge of biochemical pathways and cytoplasmic structures involved in plasmalemmal sealing might provide insights to develop treatments for traumaticThe repair（sealing） of plasmalemmal damage,consisting of small holes to complete transections,is critical for cell survival,especially for neurons that rarely regenerate cell bodies.We first describe and evaluate different measures of cell sealing.Some measures,including morphological/ultra-structural observations,membrane potential,and input resistance,provide very ambiguous assessments of plasmalemmal sealing.In contrast,measures of ionic current flow and dye barriers can,if appropriately used,provide more accurate assessments.We describe the effects of various substances（calcium,calpains,cytoskeletal proteins,ESCRT proteins,m UNC-13,NSF,PEG） and biochemical pathways（PKA,PKC,PLC,Epac,cytosolic oxidation） on plasmalemmal sealing probability,and suggest that substances,pathways,and cellular events associated with plasmalemmal sealing have undergone a very conservative evolution.During sealing,calcium ion influx mobilizes vesicles and other membranous structures（lysosomes,mitochondria,etc.） in a continuous fashion to form a vesicular plug that gradually restricts diffusion of increasingly smaller molecules and ions over a period of seconds to minutes.Furthermore,we find no direct evidence that sealing occurs through the collapse and fusion of severed plasmalemmal leaflets,or in a single step involving the fusion of one large wound vesicle with the nearby,undamaged plasmalemma.We describe how increases in perikaryal calcium levels following axonal transection account for observations that cell body survival decreases the closer an axon is transected to the perikaryon.Finally,we speculate on relationships between plasmalemmal sealing,Wallerian degeneration,and the ability of polyethylene glycol（PEG） to seal cell membranes and rejoin severed axonal ends – an important consideration for the future treatment of trauma to peripheral nerves.A better knowledge of biochemical pathways and cytoplasmic structures involved in plasmalemmal sealing might provide insights to develop treatments for traumatic

关 键 词：sealing traumatic eukaryotic vesicles axonal membranous closer biochemical vesicular muscular 

分 类 号：R741[医药卫生—神经病学与精神病学]