Logo of biochemjBJ Latest papers and much more!
Biochem J. 1998 Sep 15; 334(Pt 3): 547–551.
PMCID: PMC1219721

Specific alterations in levels of mannose 6-phosphorylated glycoproteins in different neuronal ceroid lipofuscinoses.


Mannose 6-phosphate (Man-6-P) is a carbohydrate modification that is generated on newly synthesized lysosomal proteins. This modification is specifically recognized by two Man-6-P receptors that direct the vesicular transport of the lysosomal enzymes from the Golgi to a prelysosomal compartment. The Man-6-P is rapidly removed in the lysosome of most cell types; however, in neurons the Man-6-P modification persists. In this study we have examined the spectrum of Man-6-P-containing glycoproteins in brain specimens from patients with different neuronal ceroid lipofuscinoses (NCLs), which are progressive neurodegenerative disorders with established links to defects in lysosomal catabolism. We find characteristic alterations in the Man-6-P glycoproteins in specimens from late-infantile (LINCL), juvenile (JNCL) and adult (ANCL) patients. Man-6-P glycoproteins in LINCL patients were similar to controls, with the exception that the band corresponding to CLN2, a recently identified lysosomal enzyme whose deficiency results in this disease, was absent. In an ANCL patient, two Man-6-P glycoproteins were elevated in comparison with normal controls, suggesting that this disease also results from a perturbation in lysosomal hydrolysis. In JNCL, total levels of Man-6-P glycoproteins were 7-fold those of controls. In general this was reflected by increased lysosomal enzyme activities in JNCL but three Man-6-P glycoproteins were elevated to an even greater degree. These are CLN2 and the unidentified proteins that are also highly elevated in the ANCL.

Full Text

The Full Text of this article is available as a PDF (216K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Vesa J, Hellsten E, Verkruyse LA, Camp LA, Rapola J, Santavuori P, Hofmann SL, Peltonen L. Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis. Nature. 1995 Aug 17;376(6541):584–587. [PubMed]
  • Camp LA, Hofmann SL. Purification and properties of a palmitoyl-protein thioesterase that cleaves palmitate from H-Ras. J Biol Chem. 1993 Oct 25;268(30):22566–22574. [PubMed]
  • Sleat DE, Donnelly RJ, Lackland H, Liu CG, Sohar I, Pullarkat RK, Lobel P. Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis. Science. 1997 Sep 19;277(5333):1802–1805. [PubMed]
  • Järvelä I, Sainio M, Rantamäki T, Olkkonen VM, Carpén O, Peltonen L, Jalanko A. Biosynthesis and intracellular targeting of the CLN3 protein defective in Batten disease. Hum Mol Genet. 1998 Jan;7(1):85–90. [PubMed]
  • Sleat DE, Sohar I, Lackland H, Majercak J, Lobel P. Rat brain contains high levels of mannose-6-phosphorylated glycoproteins including lysosomal enzymes and palmitoyl-protein thioesterase, an enzyme implicated in infantile neuronal lipofuscinosis. J Biol Chem. 1996 Aug 9;271(32):19191–19198. [PubMed]
  • Verkruyse LA, Hofmann SL. Lysosomal targeting of palmitoyl-protein thioesterase. J Biol Chem. 1996 Jun 28;271(26):15831–15836. [PubMed]
  • Hellsten E, Vesa J, Olkkonen VM, Jalanko A, Peltonen L. Human palmitoyl protein thioesterase: evidence for lysosomal targeting of the enzyme and disturbed cellular routing in infantile neuronal ceroid lipofuscinosis. EMBO J. 1996 Oct 1;15(19):5240–5245. [PMC free article] [PubMed]
  • Janes RW, Munroe PB, Mitchison HM, Gardiner RM, Mole SE, Wallace BA. A model for Batten disease protein CLN3: functional implications from homology and mutations. FEBS Lett. 1996 Dec 9;399(1-2):75–77. [PubMed]
  • Khan KM, Brooks SS, Pullarkat RK. Abnormal acid phosphatases in neuronal ceroid-lipofuscinoses. Am J Med Genet. 1995 Jun 5;57(2):285–289. [PubMed]
  • Pullarkat RK, Zawitosky SE. Glycoconjugate abnormalities in the ceroid-lipofuscinoses. J Inherit Metab Dis. 1993;16(2):317–322. [PubMed]
  • Valenzano KJ, Kallay LM, Lobel P. An assay to detect glycoproteins that contain mannose 6-phosphate. Anal Biochem. 1993 Feb 15;209(1):156–162. [PubMed]
  • Meunier B, Rodriguez-Lopez JN, Smith AT, Thorneley RN, Rich PR. Redox- and anion-linked protonation sites in horseradish peroxidase: analysis of distal haem pocket mutants. Biochem J. 1998 Feb 15;330(Pt 1):303–309. [PMC free article] [PubMed]
  • LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed]
  • Prasad VV, Pullarkat RK. Brain lysosomal hydrolases in neuronal ceroid-lipofuscinoses. Mol Chem Neuropathol. 1996 Oct-Dec;29(2-3):169–179. [PubMed]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem chemical compound records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records. Multiple substance records may contribute to the PubChem compound record.
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...