Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.4.4 (kinesin)
 5,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diapedesis of leukocytes across endothelial cells is a crucial step in both the innate and adaptive immune responses. Surface molecules on leukocytes and endothelial cells critical for diapedesis have been identified, but the mechanisms underlying this process are not understood. Homophilic interaction between platelet/endothelial cell adhesion molecule (PECAM) on leukocytes and PECAM at the endothelial border triggers targeted recycling of membrane from a reticulum localized close to the endothelial cell lateral border. This membrane surrounds the transmigrating leukocyte (Mamdouh, Z., X. Chen, L.M. Pierini, F.R. Maxfield, and W.A. Muller. 2003. Nature. 421:748-753). How this process occurs and whether it is required for diapedesis independent of PECAM are not known. We now report that targeted recycling from this lateral border recycling compartment (LBRC) is required for diapedesis, is mediated by kinesin family molecular motors, and requires normally functioning endothelial microtubules. Selective disruption of microtubules or inhibition of kinesin motor domain blocked targeted recycling and diapedesis of monocytes. Furthermore, targeted recycling of membrane from the LBRC was required for transmigration of lymphocytes, which migrate independently of PECAM. Thus, trafficking of membrane from the LBRC to surround leukocytes may be a general requirement for migration of leukocytes across the endothelial cell border. Furthermore, these data provide the first demonstration of a role for endothelial microtubules and kinesins in promoting diapedesis, and a mechanism to explain targeted recycling.
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PMID:Leukocyte transmigration requires kinesin-mediated microtubule-dependent membrane trafficking from the lateral border recycling compartment. 1837 93

Leukocyte migration across endothelial cell borders (paracellular) and through endothelial cells (transcellular) appear to be distinct processes. During paracellular migration, membrane from a parajunctional reticulum of interconnected vesicles, the endothelial lateral border recycling compartment (LBRC), moves to surround the leukocyte in a kinesin-mediated, microtubule-dependent manner. We show that transcellular migration likewise requires targeted trafficking of LBRC membrane. We show that in addition to platelet/endothelial cell adhesion molecule (PECAM; CD31), CD99 and junctional adhesion molecule A (JAM-A), but apparently not vascular endothelial cell-specific cadherin (cadherin 5, CD144), are components of the LBRC. During transcellular migration, LBRC membrane invests the transmigrating leukocyte. Intracellular adhesion molecule 1 (ICAM-1) on the apical endothelial surface is enriched around adherent leukocytes. Depolymerization of microtubules has no effect on ICAM-1 enrichment but blocks targeted trafficking of LBRC membrane and transcellular migration by >90%. Similar to their effects on paracellular transmigration, antibodies against PECAM or CD99, but not JAM-A, block transcellular migration. We conclude that similar molecular mechanisms promote both para- and transcellular migration.
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PMID:Transcellular migration of leukocytes is mediated by the endothelial lateral border recycling compartment. 1988 95

Leukocytes attach to vascular endothelial cells at the site of inflammation via a series of intercellular adhesive interactions. In a separate step in leukocyte extravasation, transendothelial migration is regulated by molecules that play no role in the preceding steps of tethering, rolling, adhesion, and locomotion. Transendothelial migration itself can be dissected into a series of distinct interactions regulated sequentially by molecules concentrated at the endothelial cell border; these include platelet/endothelial cell adhesion molecule, poliovirus receptor (CD155), and CD99. These molecules are components of the lateral border recycling compartment (LBRC), a perijunctional network of interconnected tubulovesicular membrane that traffics to surround the leukocyte as it passes across the endothelial cell. This targeted recycling of LBRC requires kinesin to move the membrane along microtubules, and interfering with LBRC trafficking blocks transmigration of neutrophils, monocytes, and lymphocytes. The LBRC is also recruited to mediate transcellular migration when that occurs. Movement of the LBRC is coordinated with events on the luminal surface, such as clustering of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 under the migrating leukocyte, as well as movement of vascular endothelial cadherin and its associated catenins out of the junction at the site of transendothelial migration. How these events are coordinated is not known, but their regulation shares common signaling pathways that may serve to connect these steps.
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PMID:How endothelial cells regulate transmigration of leukocytes in the inflammatory response. 2465 76