cDNA and genomic cloning of lacritin, a novel secretion enhancing factor from the human lacrimal gland11Edited by J. Karn

Sanghi, Sandhya; Kumar, Rajesh; Lumsden, A.J.; Dickinson, Douglas; Klepeis, Veronica E.; Trinkaus‐Randall, Vickery; Frierson, Henry F.; Laurie, Gordon W.

doi:10.1006/jmbi.2001.4748

Cited by 77 publications

(122 citation statements)

References 62 publications

(55 reference statements)

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“…DCD encodes a secreted protein with limited homology to lacritin and an EST. Lacritin is a secretionenhancing and growth-promoting factor recently identified from lacrimal gland (24). The EST is expressed in the cerebral cortex, and it encodes an uncharacterized protein containing a repetitive sequence (ETPA) found in several secreted proteins.…”

Section: Discussionmentioning

confidence: 99%

A neural survival factor is a candidate oncogene in breast cancer

Porter

Weremowicz

Chin

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

124

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Using serial analysis of gene expression (SAGE), we identified a SAGE tag that was present only in invasive breast carcinomas and their lymph node metastases. The transcript corresponding to this SAGE tag, dermcidin (DCD), encodes a secreted protein normally expressed only in the pons of the brain and sweat glands. Array comparative genomic hybridization, fluorescence in situ hybridization, and immunohistochemical analyses determined that DCD is overexpressed in Ϸ10% of invasive breast carcinomas; in some cases its overexpression is coupled with a focal copy number gain of its locus at 12q13.1, and its expression is associated with advanced clinical stage and poor prognosis. Expression of DCD in breast cancer cells promotes cell growth and survival and reduces serum dependency. Putative high-and low-affinity receptors for DCD are present on the cell surface of breast carcinomas and neurons of the brain. Based on these data we hypothesize that DCD may play a role in tumorigenesis by means of enhancing cell growth and survival in a subset of breast carcinomas.

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Section: Discussionmentioning

confidence: 99%

A neural survival factor is a candidate oncogene in breast cancer

Porter

Weremowicz

Chin

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

124

126

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“…Most lacritin is generated by lacrimal gland from which it is apically released via acinar cell secretory granules to transit through ducts onto the ocular surface (Sanghi et al, 2001). Lacritin also appears to be a product of meibomian gland (Tsai et al, 2006).…”

Section: Functionmentioning

confidence: 99%

“…It is 1 of 29 'lacrimal-preferred genes' and the 6 th most common mRNA in NEIBank's human lacrimal EST database. Lacritin appears to promote constitutive tear secretion in cultured lacrimal acinar cells, possibly via an autocrine stimulatory mechanism (Sanghi et al, 2001). Lacritin also stimulates human corneal epithelial (HCE-T) cell proliferation via a biphasic 1 -10 nM dose optimum, but has no apparent mitogenic effect on fibroblasts, glia or erythroleukemic cells, and epithelia from epidermis, breast cancer, melanoma or testes (Wang et al, 2006).…”

Section: Functionmentioning

confidence: 99%

Focus on Molecules: Lacritin

Wang

McKown

et al. 2008

Experimental Eye Research

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“…These LG acinar cells produce a diverse array of secretory proteins that are internally sorted into large pools of serous and mucous secretory vesicles (SV) sized ϳ1 m in diameter and stored beneath the apical plasma membrane (APM) in preparation for regulated exocytosis. SV contents include nutrients and growth factors (lacritin and EGF), antibacterial and antiviral factors (secretory IgA and lactoferrin), and an array of proteases and lysosomal hydrolases (10,39,47). Despite its physiological importance, however, few studies have focused on the mechanisms of secretory membrane trafficking in LG acinar cells, in part due to the fragility and heterogeneity of these LG acinar SV relative to those in other acinar secretory cells, e.g., pancreatic acini (7).…”

mentioning

confidence: 99%

Rab27b regulates exocytosis of secretory vesicles in acinar epithelial cells from the lacrimal gland

Chiang¹,

Ngo²,

Schechter

et al. 2011

American Journal of Physiology-Cell Physiology

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mechanisms largely yet uncharacterized. We investigated the role of Rab27b in the terminal release of these secretory vesicles. Confocal fluorescence microscopy analysis of primary cultured rabbit lacrimal gland acinar cells revealed that Rab27b was enriched on the membrane of large subapical vesicles that were significantly colocalized with Rab3D and Myosin 5C. Stimulation of cultured acinar cells with the secretagogue carbachol resulted in apical fusion of these secretory vesicles with the plasma membrane. Evaluation of morphological changes by transmission electron microscopy of lacrimal glands from Rab27b Ϫ/Ϫ and Rab27 ash/ash /Rab27b Ϫ/Ϫ mice, but not ashen mice deficient in Rab27a, showed changes in abundance and organization of secretory vesicles, further confirming a role for this protein in secretory vesicle exocytosis. Glands lacking Rab27b also showed increased lysosomes, damaged mitochondria, and autophagosomelike organelles. In vitro, expression of constitutively active Rab27b increased the average size but retained the subapical distribution of Rab27b-enriched secretory vesicles, whereas dominant-negative Rab27b redistributed this protein from membrane to the cytoplasm. Functional studies measuring release of a cotransduced secretory protein, syncollin-GFP, showed that constitutively active Rab27b enhanced, whereas dominant-negative Rab27b suppressed, stimulated release. Disruption of actin filaments inhibited vesicle fusion to the apical membrane but did not disrupt homotypic fusion. These data show that Rab27b participates in aspects of lacrimal gland acinar cell secretory vesicle formation and release. actin; Rab3d; exocrine secretion; syncollin; mouse models A FUNCTIONING LACRIMAL GLAND (LG) is critical for a healthy ocular surface. This exocrine gland is the primary source of tear proteins and fluid, which, released up on the gland's exposure to sympathetic or parasympathetic agonists provided by innervating nerves, contribute to the middle aqueous layer of the precorneal film. Much of the LG's secretions originate from acinar cells, which constitute over 80% of the mass of the LG (13). These LG acinar cells produce a diverse array of secretory proteins that are internally sorted into large pools of serous and mucous secretory vesicles (SV) sized ϳ1 m in diameter and stored beneath the apical plasma membrane (APM) in preparation for regulated exocytosis. SV contents include nutrients and growth factors (lacritin and EGF), antibacterial and antiviral factors (secretory IgA and lactoferrin), and an array of proteases and lysosomal hydrolases (10, 39, 47). Despite its physiological importance, however, few studies have focused on the mechanisms of secretory membrane trafficking in LG acinar cells, in part due to the fragility and heterogeneity of these LG acinar SV relative to those in other acinar secretory cells, e.g., pancreatic acini (7).The current schematic of exocytosis in the LG acinar cell suggests multiple participants. Mature LG acinar cell SV localize beneath an actin-rich network und...

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cDNA and genomic cloning of lacritin, a novel secretion enhancing factor from the human lacrimal gland11Edited by J. Karn

Cited by 77 publications

References 62 publications

A neural survival factor is a candidate oncogene in breast cancer

A neural survival factor is a candidate oncogene in breast cancer

Focus on Molecules: Lacritin

Rab27b regulates exocytosis of secretory vesicles in acinar epithelial cells from the lacrimal gland

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